Multidetector row CT for imaging the paediatric tracheobronchial tree

The introduction of multidetector row computed tomography (MDCT) scanners has altered the approach to imaging the paediatric thorax. In an environment where the rapid acquisition of CT data allows general hospitals to image children instead of referring them to specialist paediatric centres, it is vital that general radiologists have access to protocols appropriate for paediatric applications. Thus a dramatic reduction in the delivered radiation dose is ensured with optimal contrast bolus delivery and timing, and inappropriate repetition of the scans is avoided. This article focuses on the main principles of volumetric CT imaging that apply generically to all MDCT scanners. We describe the reconstruction techniques for imaging the paediatric thorax and the low-dose protocols used in our institution on a 16-slice detector CT scanner. Examples of the commonest clinical applications are also given

Stereology as the 3D tool to quantitate lung architecture

Stereology is the method of choice for the quantitative assessment of biological objects in microscopy. It takes into account the fact that, in traditional microscopy such as conventional light and transmission electron microscopy, although one has to rely on measurements on nearly two-dimensional sections from fixed and embedded tissue samples, the quantitative data obtained by these measurements should characterize the real three-dimensional properties of the biological objects and not just their "flatland" appearance on the sections. Thus, three-dimensionality is a built-in property of stereological sampling and measurement tools. Stereology is, therefore, perfectly suited to be combined with 3D imaging techniques which cover a wide range of complementary sample sizes and resolutions, e.g. micro-computed tomography, confocal microscopy and volume electron microscopy. Here, we review those stereological principles that are of particular relevance for 3D imaging and provide an overview of applications of 3D imaging-based stereology to the lung in health and disease. The symbiosis of stereology and 3D imaging thus provides the unique opportunity for unbiased and comprehensive quantitative characterization of the three-dimensional architecture of the lung from macro to nano scale

X-ray-based virtual slicing of TB-infected lungs

Hollow organs such as the lungs pose a considerable challenge for post-mortem imaging in preclinical research owing to their extremely low contrast and high structural complexity. The aim of our study was to enhance the contrast of tuberculosis lesions for their stratification by 3D x-ray&-based virtual slicing. Organ samples were taken from five control and five tuberculosis-infected mice. Micro-Computed Tomography (CT) scans of the subjects were acquired in vivo (without contrast agent) and post-mortem (with contrast agent). The proposed contrast-enhancing technique consists of x-ray contrast agent uptake (silver nitrate and iodine) by immersion. To create the histology ground-truth, the CT scan of the paraffin block guided the sectioning towards specific planes of interest. The digitalized histological slides reveal the presence, extent, and appearance of the contrast agents in lung structures and organized aggregates of immune cells. These findings correlate with the contrast-enhanced micro-CT slice. The abnormal densities in the lungs due to tuberculosis disease are concentrated in the right tail of the lung intensity histograms. The increase in the width of the right tail (~376%) indicates a contrast enhancement of the details of the abnormal densities. Postmortem contrast agents enhance the x-ray attenuation in tuberculosis lesions to allow 3D visualization by polychromatic x-ray CT, providing an advantageous tool for virtual slicing of whole lungs. The proposed contrast-enhancing technique combined with computational methods and the diverse micro-CT modalities will open the doors to the stratification of lesion types associated with infectious diseases.The research leading to these results received funding from the Innovative Medicines Initiative (www.imi.europa.eu) Joint Undertaking under grant agreement no. 115337, whose resources comprise funding from the European Union Seventh Framework Programme (FP7/2007–2013) and EFPIA companies in kind contribution. This work was partially funded by projects RTC-2015-3772-1, TEC2015-73064-EXP and TEC2016-78052-R from the Spanish Ministry of Economy, TOPUS S2013/MIT-3024 project from the regional government of Madrid and by the Department of Health, UK. This study (was supported by the Instituto de Salud Carlos III (Plan Estatal de I + D + i 2013–2016) and co-financed by the European Social Fund (ESF) “ESF investing in your future”. The authors thank Dr.Guembe from CIMA-Universidad de Navarra for preparing and staining the tissue sections, and to Dr. Guerrero-Aspizua and Prof. Conti of the Department of Bioengineering, Universidad Carlos III de Madrid for the pathology evaluation

Robust, Standardized Quantification of Pulmonary Emphysema in Low Dose CT Exams

RATIONALE AND OBJECTIVES: The aim of this study was to present and evaluate a fully automated system for emphysema quantification on low-dose computed tomographic images. The platform standardizes emphysema measurements against changes in the reconstruction algorithm and slice thickness. MATERIALS AND METHODS: Emphysema was quantified in 149 patients using a fully automatic, in-house developed software (the Robust Automatic On-Line Pulmonary Helper). The accuracy of the system was evaluated against commercial software, and its reproducibility was assessed using pairs of volume-corrected images taken 1 year apart. Furthermore, to standardize quantifications, the effect of changing the reconstruction parameters was modeled using a nonlinear fit, and the inverse of the model function was then applied to the data. The association between quantifications and pulmonary function testing was also evaluated. The accuracy of the in-house software compared to that of commercial software was measured using Spearman's rank correlation coefficient, the mean difference, and the intrasubject variability. Agreement between the methods was studied using Bland-Altman plots. To assess the reproducibility of the method, intraclass correlation coefficients and Bland-Altman plots were used. The statistical significance of the differences between the standardized data and the reference data (soft-tissue reconstruction algorithm B40f; slice thickness, 1 mm) was assessed using a paired two-sample t test. RESULTS: The accuracy of the method, measured as intrasubject variability, was 3.86 mL for pulmonary volume, 0.01% for emphysema index, and 0.39 Hounsfield units for mean lung density. Reproducibility, assessed using the intraclass correlation coefficient, was >0.95 for all measurements. The standardization method applied to compensate for variations in the reconstruction algorithm and slice thickness increased the intraclass correlation coefficients from 0.87 to 0.97 and from 0.99 to 1.00, respectively. The correlation of the standardized measurements with pulmonary function testing parameters was similar to that of the reference (for the emphysema index and the obstructive subgroup: forced expiratory volume in 1 second, -0.647% vs -0.615%; forced expiratory volume in 1 second/forced vital capacity, -0.672% vs -0.654%; and diffusing capacity for carbon monoxide adjusted for hemoglobin concentration, -0.438% vs -0.523%). CONCLUSIONS: The new emphysema quantification method presented in this report is accurate and reproducible and, thanks to its standardization method, robust to changes in the reconstruction parameters

3-D lung deformation and function from respiratory-gated 4-D x-ray CT images : application to radiation treatment planning.

Many lung diseases or injuries can cause biomechanical or material property changes that can alter lung function. While the mechanical changes associated with the change of the material properties originate at a regional level, they remain largely asymptomatic and are invisible to global measures of lung function until they have advanced significantly and have aggregated. In the realm of external beam radiation therapy of patients suffering from lung cancer, determination of patterns of pre- and post-treatment motion, and measures of regional and global lung elasticity and function are clinically relevant. In this dissertation, we demonstrate that 4-D CT derived ventilation images, including mechanical strain, provide an accurate and physiologically relevant assessment of regional pulmonary function which may be incorporated into the treatment planning process. Our contributions are as follows: (i) A new volumetric deformable image registration technique based on 3-D optical flow (MOFID) has been designed and implemented which permits the possibility of enforcing physical constraints on the numerical solutions for computing motion field from respiratory-gated 4-D CT thoracic images. The proposed optical flow framework is an accurate motion model for the thoracic CT registration problem. (ii) A large displacement landmark-base elastic registration method has been devised for thoracic CT volumetric image sets containing large deformations or changes, as encountered for example in registration of pre-treatment and post-treatment images or multi-modality registration. (iii) Based on deformation maps from MOFIO, a novel framework for regional quantification of mechanical strain as an index of lung functionality has been formulated for measurement of regional pulmonary function. (iv) In a cohort consisting of seven patients with non-small cell lung cancer, validation of physiologic accuracy of the 4-0 CT derived quantitative images including Jacobian metric of ventilation, Vjac, and principal strains, (V?1, V?2, V?3, has been performed through correlation of the derived measures with SPECT ventilation and perfusion scans. The statistical correlations with SPECT have shown that the maximum principal strain pulmonary function map derived from MOFIO, outperforms all previously established ventilation metrics from 40-CT. It is hypothesized that use of CT -derived ventilation images in the treatment planning process will help predict and prevent pulmonary toxicity due to radiation treatment. It is also hypothesized that measures of regional and global lung elasticity and function obtained during the course of treatment may be used to adapt radiation treatment. Having objective methods with which to assess pre-treatment global and regional lung function and biomechanical properties, the radiation treatment dose can potentially be escalated to improve tumor response and local control

Development and validation of HRCT airway segmentation algorithms

Direct measurements of airway lumen and wall areas are potentially useful as a diagnostic tool and as an aid to understanding the pathophysiology underlying lung disease. Direct measurements can be made from images created by high resolution computer tomography (HRCT) by using computer-based algorithms to segment airways, but current validation techniques cannot adequately establish the accuracy and precision of these algorithms. A detailed review of HRCT airway segmentation algorithms was undertaken, from which three candidate algorithm designs were developed. A custom Windows-based software program was implemented to facilitate multi-modality development and validation of the segmentation algorithms. The performance of the algorithms was examined in clinical HRCT images. A centre-likelihood (CL) ray-casting algorithm was found to be the most suitable algorithm due to its speed and reliability in semi-automatic segmentation and tracking of the airway wall. Several novel refinements were demonstrated to improve the CL algorithm’s robustness in HRCT lung data. The performance of the CL algorithm was then quantified in two-dimensional simulated data to optimise customisable parameters such as edge-detection method, interpolation and number of rays. Novel correction equations to counter the effects of volume averaging and airway orientation angle were derived and demonstrated in three-dimensional simulated data. The optimal CL algorithm was validated with HRCT data using a plastic phantom and a pig lung phantom matched to micro-CT. Accuracy was found to be improved compared to previous studies using similar methods. The volume averaging correction was found to improve precision and accuracy in the plastic phantom but not in the pig lung phantom. When tested in a clinical setting the results of the optimised CL algorithm was in agreement with the results of other measures of lung function. The thesis concludes that the relative contributions of confounders of airway measurement have been quantified in simulated data and the CL algorithm’s performance has been validated in a plastic phantom as well as animal model. This validation protocol has improved the accuracy and precision of measurements made using the CL algorith