Caiyun Wu

Chest Fat Quantification via CT Based on Standardized Anatomy Space in Adult Lung Transplant Candidates

Purpose Overweight and underweight conditions are considered relative contraindications to lung transplantation due to their association with excess mortality. Yet, recent work suggests that body mass index (BMI) does not accurately reflect adipose tissue mass in adults with advanced lung diseases. Alternative and more accurate measures of adiposity are needed. Chest fat estimation by routine computed tomography (CT) imaging may therefore be important for identifying high-risk lung transplant candidates. In this paper, an approach to chest fat quantification and quality assessment based on a recently formulated concept of standardized anatomic space (SAS) is presented. The goal of the paper is to seek answers to several key questions related to chest fat quantity and quality assessment based on a single slice CT (whether in the chest, abdomen, or thigh) versus a volumetric CT, which have not been addressed in the literature. Methods Unenhanced chest CT image data sets from 40 adult lung transplant candidates (age 58 ± 12 yrs and BMI 26.4 ± 4.3 kg/m2), 16 with chronic obstructive pulmonary disease (COPD), 16 with idiopathic pulmonary fibrosis (IPF), and the remainder with other conditions were analyzed together with a single slice acquired for each patient at the L5 vertebral level and mid-thigh level. The thoracic body region and the interface between subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in the chest were consistently defined in all patients and delineated using Live Wire tools. The SAT and VAT components of chest were then segmented guided by this interface. The SAS approach was used to identify the corresponding anatomic slices in each chest CT study, and SAT and VAT areas in each slice as well as their whole volumes were quantified. Similarly, the SAT and VAT components were segmented in the abdomen and thigh slices. Key parameters of the attenuation (Hounsfield unit (HU) distributions) were determined from each chest slice and from the whole chest volume separately for SAT and VAT components. The same parameters were also computed from the single abdominal and thigh slices. The ability of the slice at each anatomic location in the chest (and abdomen and thigh) to act as a marker of the measures derived from the whole chest volume was assessed via Pearson correlation coefficient (PCC) analysis. Results The SAS approach correctly identified slice locations in different subjects in terms of vertebral levels. PCC between chest fat volume and chest slice fat area was maximal at the T8 level for SAT (0.97) and at the T7 level for VAT (0.86), and was modest between chest fat volume and abdominal slice fat area for SAT and VAT (0.73 and 0.75, respectively). However, correlation was weak for chest fat volume and thigh slice fat area for SAT and VAT (0.52 and 0.37, respectively), and for chest fat volume for SAT and VAT and BMI (0.65 and 0.28, respectively). These same single slice locations with maximal PCC were found for SAT and VAT within both COPD and IPF groups. Most of the attenuation properties derived from the whole chest volume and single best chest slice for VAT (but not for SAT) were significantly different between COPD and IPF groups. Conclusions This study demonstrates a new way of optimally selecting slices whose measurements may be used as markers of similar measurements made on the whole chest volume. The results suggest that one or two slices imaged at T7 and T8 vertebral levels may be enough to estimate reliably the total SAT and VAT components of chest fat and the quality of chest fat as determined by attenuation distributions in the entire chest volume.

Minimally interactive segmentation of 4D dynamic upper airway MR images via fuzzy connectedness.

PURPOSE There are several disease conditions that lead to upper airway restrictive disorders. In the study of these conditions, it is important to take into account the dynamic nature of the upper airway. Currently, dynamic magnetic resonance imaging is the modality of choice for studying these diseases. Unfortunately, the contrast resolution obtainable in the images poses many challenges for an effective segmentation of the upper airway structures. No viable methods have been developed to date to solve this problem. In this paper, the authors demonstrate a practical solution by employing an iterative relative fuzzy connectedness delineation algorithm as a tool. METHODS 3D dynamic images were collected at ten equally spaced instances over the respiratory cycle (i.e., 4D) in 20 female subjects with obstructive sleep apnea syndrome. The proposed segmentation approach consists of the following steps. First, image background nonuniformities are corrected which is then followed by a process to correct for the nonstandardness of MR image intensities. Next, standardized image intensity statistics are gathered for the nasopharynx and oropharynx portions of the upper airway as well as the surrounding soft tissue structures including air outside the body region, hard palate, soft palate, tongue, and other soft structures around the airway including tonsils (left and right) and adenoid. The affinity functions needed for fuzzy connectedness computation are derived based on these tissue intensity statistics. In the next step, seeds for fuzzy connectedness computation are specified for the airway and the background tissue components. Seed specification is needed in only the 3D image corresponding to the first time instance of the 4D volume; from this information, the 3D volume corresponding to the first time point is segmented. Seeds are automatically generated for the next time point from the segmentation of the 3D volume corresponding to the previous time point, and the process continues and runs without human interaction and completes in 10 s for segmenting the airway structure in the whole 4D volume. RESULTS Qualitative evaluations performed to examine smoothness and continuity of motions of the entire upper airway as well as its transverse sections at critical anatomic locations indicate that the segmentations are consistent. Quantitative evaluations of the separate 200 3D volumes and the 20 4D volumes yielded true positive and false positive volume fractions around 95% and 0.1%, respectively, and mean boundary placement errors under 0.5 mm. The method is robust to variations in the subjective action of seed specification. Compared with a segmentation approach based on a registration technique to propagate segmentations, the proposed method is more efficient, accurate, and less prone to error propagation from one respiratory time point to the next. CONCLUSIONS The proposed method is the first demonstration of a viable and practical approach for segmenting the upper airway structures in dynamic MR images. Compared to registration-based methods, it effectively reduces error propagation and consequently achieves not only more accurate segmentations but also more consistent motion representation in the segmentations. The method is practical, requiring minimal user interaction and computational time.

Interactive iterative relative fuzzy connectedness lung segmentation on thoracic 4D dynamic MR images

Lung delineation via dynamic 4D thoracic magnetic resonance imaging (MRI) is necessary for quantitative image analysis for studying pediatric respiratory diseases such as thoracic insufficiency syndrome (TIS). This task is very challenging because of the often-extreme malformations of the thorax in TIS, lack of signal from bone and connective tissues resulting in inadequate image quality, abnormal thoracic dynamics, and the inability of the patients to cooperate with the protocol needed to get good quality images. We propose an interactive fuzzy connectedness approach as a potential practical solution to this difficult problem. Manual segmentation is too labor intensive especially due to the 4D nature of the data and can lead to low repeatability of the segmentation results. Registration-based approaches are somewhat inefficient and may produce inaccurate results due to accumulated registration errors and inadequate boundary information. The proposed approach works in a manner resembling the Iterative Livewire tool but uses iterative relative fuzzy connectedness (IRFC) as the delineation engine. Seeds needed by IRFC are set manually and are propagated from slice-to-slice, decreasing the needed human labor, and then a fuzzy connectedness map is automatically calculated almost instantaneously. If the segmentation is acceptable, the user selects “next” slice. Otherwise, the seeds are refined and the process continues. Although human interaction is needed, an advantage of the method is the high level of efficient user-control on the process and non-necessity to refine the results. Dynamic MRI sequences from 5 pediatric TIS patients involving 39 3D spatial volumes are used to evaluate the proposed approach. The method is compared to two other IRFC strategies with a higher level of automation. The proposed method yields an overall true positive and false positive volume fraction of 0.91 and 0.03, respectively, and Hausdorff boundary distance of 2 mm.

Retrospective 4D MR image construction from free-breathing slice Acquisitions: A novel graph-based approach.

Purpose: Dynamic or 4D imaging of the thorax has many applications. Both prospective and retrospective respiratory gating and tracking techniques have been developed for 4D imaging via CT and MRI. For pediatric imaging, due to radiation concerns, MRI becomes the de facto modality of choice. In thoracic insufficiency syndrome (TIS), patients often suffer from extreme malformations of the chest wall, diaphragm, and/or spine with inability of the thorax to support normal respiration or lung growth (Campbell et al., 2003, Campbell and Smith, 2007), as such patient cooperation needed by some of the gating and tracking techniques are difficult to realize without causing patient discomfort and interference with the breathing mechanism itself. Therefore (ventilator‐supported) free‐breathing MRI acquisition is currently the best choice for imaging these patients. This, however, raises a question of how to create a consistent 4D image from such acquisitions. This paper presents a novel graph‐based technique for compiling the best 4D image volume representing the thorax over one respiratory cycle from slice images acquired during unencumbered natural tidal‐breathing of pediatric TIS patients. Methods: In our approach, for each coronal (or sagittal) slice position, images are acquired at a rate of about 200–300 ms/slice over several natural breathing cycles which yields over 2000 slices. A weighted graph is formed where each acquired slice constitutes a node and the weight of the arc between two nodes defines the degree of contiguity in space and time of the two slices. For each respiratory phase, an optimal 3D spatial image is constructed by finding the best path in the graph in the spatial direction. The set of all such 3D images for a given respiratory cycle constitutes a 4D image. Subsequently, the best 4D image among all such constructed images is found over all imaged respiratory cycles. Two types of evaluation studies are carried out to understand the behavior of this algorithm and in comparison to a method called Random Stacking – a 4D phantom study and 10 4D MRI acquisitions from TIS patients and normal subjects. The 4D phantom was constructed by 3D printing the pleural spaces of an adult thorax, which were segmented in a breath‐held MRI acquisition. Results: Qualitative visual inspection via cine display of the slices in space and time and in 3D rendered form showed smooth variation for all data sets constructed by the proposed method. Quantitative evaluation was carried out to measure spatial and temporal contiguity of the slices via segmented pleural spaces. The optimal method showed smooth variation of the pleural space as compared to Random Stacking whose behavior was erratic. The volumes of the pleural spaces at the respiratory phase corresponding to end inspiration and end expiration were compared to volumes obtained from breath‐hold acquisitions at roughly the same phase. The mean difference was found to be roughly 3%. Conclusions: The proposed method is purely image‐based and post‐hoc and does not need breath holding or external surrogates or instruments to record respiratory motion or tidal volume. This is important and practically warranted for pediatric patients. The constructed 4D images portray spatial and temporal smoothness that should be expected in a consistent 4D volume. We believe that the method can be routinely used for thoracic 4D imaging. Graphical abstract Figure. Image, graphical abstract HighlightsFree‐breathing MRI slice acquisition of pediatric thoraces with ailments.Novel globally optimal graph‐based method of 4D construction from 1000s of slices.Image‐based strategy without the need for breath holding or external surrogates.Consistent and temporally and spatially smooth 4D constructed image.4D phantom experiment based on 3D printing of a patient thorax for validation.

Fat segmentation on chest CT images via fuzzy models

Quantification of fat throughout the body is vital for the study of many diseases. In the thorax, it is important for lung transplant candidates since obesity and being underweight are contraindications to lung transplantation given their associations with increased mortality. Common approaches for thoracic fat segmentation are all interactive in nature, requiring significant manual effort to draw the interfaces between fat and muscle with low efficiency and questionable repeatability. The goal of this paper is to explore a practical way for the segmentation of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) components of chest fat based on a recently developed body-wide automatic anatomy recognition (AAR) methodology. The AAR approach involves 3 main steps: building a fuzzy anatomy model of the body region involving all its major representative objects, recognizing objects in any given test image, and delineating the objects. We made several modifications to these steps to develop an effective solution to delineate SAT/VAT components of fat. Two new objects representing interfaces of SAT and VAT regions with other tissues, SatIn and VatIn are defined, rather than using directly the SAT and VAT components as objects for constructing the models. A hierarchical arrangement of these new and other reference objects is built to facilitate their recognition in the hierarchical order. Subsequently, accurate delineations of the SAT/VAT components are derived from these objects. Unenhanced CT images from 40 lung transplant candidates were utilized in experimentally evaluating this new strategy. Mean object location error achieved was about 2 voxels and delineation error in terms of false positive and false negative volume fractions were, respectively, 0.07 and 0.1 for SAT and 0.04 and 0.2 for VAT.

Architectural analysis on dynamic MRI to study thoracic insufficiency syndrome

The major hurdles currently preventing advance and innovation in thoracic insufficiency syndrome (TIS) assessment and treatment are the lack of standardizable objective diagnostic measurement techniques that describe the 3D thoracoabdominal structures and the dynamics of respiration. Our goal is to develop, test, and evaluate a quantitative dynamic magnetic resonance imaging (QdMRI) methodology and a biomechanical understanding for deriving key quantitative parameters from free-tidal-breathing dMRI image data for describing the 3D structure and dynamics of the thoracoabdominal organs of TIS patients. In this paper, we propose an idea of a shape sketch to codify and then quantify the overall thoracic architecture, which involves the selection of 3D landmark points and computation of 3D dynamic distances over a respiratory cycle. We perform two statistical analyses of distance sketches on 25 different TIS patients to try to understand the pathophysiological mechanisms in relation to spine deformity and to quantitatively evaluate improvements from pre-operative to post-operative states. This QdMRI methodology involves developing: (1) a 4D image construction method; (2) an algorithm for the 4D segmentation of thoraco-abdominal structures; and (3) a set of key quantitative parameters. We illustrate that the TIS dynamic distance analysis method produces results previously unknown and precisely describes the morphologic and dynamic alterations of the thorax in TIS. A set of 3D thoracoabdominal distances and/or distance differences enables the precise estimation of key measures such as left & right differences, differences over tidal breathing, and differences from pre- to post-operative condition.

Quantitative analysis of adipose tissue on chest CT to predict primary graft dysfunction in lung transplant recipients: a novel optimal biomarker approach

In this study, patients who underwent lung transplantation are categorized into two groups of successful (positive) or failed (negative) transplantations according to primary graft dysfunction (PGD), i.e., acute lung injury within 72 hours of lung transplantation. Obesity or being underweight is associated with an increased risk of PGD. Adipose quantification and characterization via computed tomography (CT) imaging is an evolving topic of interest. However, very little research of PGD prediction using adipose quantity or characteristics derived from medical images has been performed. The aim of this study is to explore image-based features of thoracic adipose tissue on pre-operative chest CT to distinguish between the above two groups of patients. 140 unenhanced chest CT images from three lung transplant centers (Columbia, Penn, and Duke) are included in this study. 124 patients are in the successful group and 16 in failure group. Chest CT slices at the T7 and T8 vertebral levels are captured to represent the thoracic fat burden by using a standardized anatomic space (SAS) approach. Fat (subcutaneous adipose tissue (SAT)/ visceral adipose tissue (VAT)) intensity and texture properties (1142 in total) for each patient are collected, and then an optimal feature set is selected to maximize feature independence and separation between the two groups. Leave-one-out and leave-ten-out crossvalidation strategies are adopted to test the prediction ability based on those selected features all of which came from VAT texture properties. Accuracy of prediction (ACC), sensitivity (SEN), specificity (SPE), and area under the curve (AUC) of 0.87/0.97, 0.87/0.97, 0.88/1.00, and 0.88/0.99, respectively are achieved by the method. The optimal feature set includes only 5 features (also all from VAT), which might suggest that thoracic VAT plays a more important role than SAT in predicting PGD in lung transplant recipients.

Lung parenchymal analysis on dynamic MRI in thoracic insufficiency syndrome to assess changes following surgical intervention

General surgeons, orthopedists, and pulmonologists individually treat patients with thoracic insufficiency syndrome (TIS). The benefits of growth-sparing procedures such as Vertical Expandable Prosthetic Titanium Rib (VEPTR)insertionfor treating patients with TIS have been demonstrated. However, at present there is no objective assessment metricto examine different thoracic structural components individually as to their roles in the syndrome, in contributing to dynamics and function, and in influencing treatment outcome. Using thoracic dynamic MRI (dMRI), we have been developing a methodology to overcome this problem. In this paper, we extend this methodology from our previous structural analysis approaches to examining lung tissue properties. We process the T2-weighted dMRI images through a series of steps involving 4D image construction of the acquired dMRI images, intensity non-uniformity correction and standardization of the 4D image, lung segmentation, and estimation of the parameters describing lung tissue intensity distributions in the 4D image. Based on pre- and post-operative dMRI data sets from 25 TIS patients (predominantly neuromuscular and congenital conditions), we demonstrate how lung tissue can be characterized by the estimated distribution parameters. Our results show that standardized T2-weighted image intensity values decrease from the pre- to post-operative condition, likely reflecting improved lung aeration post-operatively. In both pre- and post-operative conditions, the intensity values decrease also from end-expiration to end-inspiration, supporting the basic premise of our results.

Quantitative dynamic MRI (QdMRI) volumetric analysis of pediatric patients with thoracic insufficiency syndrome

The lack of standardizable objective diagnostic measurement techniques is a major hurdle in the assessment and treatment of pediatric patients with thoracic insufficiency syndrome (TIS). The aim of this paper is to explore quantitative dynamic MRI (QdMRI) volumetric parameters derived from thoracic dMRI in pediatric patients with TIS and the relationships between dMRI parameters and clinical measurements. 25 TIS patients treated with vertical expandable prosthetic titanium rib (VEPTR) surgery are included in this retrospective study. Left and right lungs at endinspiration and end-expiration are segmented from constructed 4D dMRI images. Lung volumes and excursion (or tidal) volumes of the left/right chest wall and hemi-diaphragms are computed. Commonly used clinical parameters include thoracic and lumbar Cobb angles and respiratory measurements from pulmonary function testing (PFT). 200 3D lungs in total (left & right, pre-operative & post-operative, end-inspiration & end-expiration) are segmented for analysis. Our analysis indicates that change of resting breathing rate (RR) following surgery is negatively correlated with that of QdMRI parameters. Chest wall tidal volumes and hemi-diaphragm tidal volumes increase significantly following surgery. Clinical parameter RR reduced after surgical treatment with P values around 0.06 but no significant differences were found on other clinical parameters. The significant increase in post-operative tidal volumes suggests a treatment-related improvement in lung capacity. The reduction of RR following surgery shows that breathing function is improved. The QdMRI parameters may offer an objective marker set for studying TIS, which is currently lacking.

Disease quantification on PET/CT images without object delineation

The derivation of quantitative information from images to make quantitative radiology (QR) clinically practical continues to face a major image analysis hurdle because of image segmentation challenges. This paper presents a novel approach to disease quantification (DQ) via positron emission tomography/computed tomography (PET/CT) images that explores how to decouple DQ methods from explicit dependence on object segmentation through the use of only object recognition results to quantify disease burden. The concept of an object-dependent disease map is introduced to express disease severity without performing explicit delineation and partial volume correction of either objects or lesions. The parameters of the disease map are estimated from a set of training image data sets. The idea is illustrated on 20 lung lesions and 20 liver lesions derived from 18F-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT scans of patients with various types of cancers and also on 20 NEMA PET/CT phantom data sets. Our preliminary results show that, on phantom data sets, “disease burden” can be estimated to within 2% of known absolute true activity. Notwithstanding the difficulty in establishing true quantification on patient PET images, our results achieve 8% deviation from “true” estimates, with slightly larger deviations for small and diffuse lesions where establishing ground truth becomes really questionable, and smaller deviations for larger lesions where ground truth set up becomes more reliable. We are currently exploring extensions of the approach to include fully automated body-wide DQ, extensions to just CT or magnetic resonance imaging (MRI) alone, to PET/CT performed with radiotracers other than FDG, and other functional forms of disease maps.