Thoracic insufficiency syndrome: Approaches to assessment and management.

Thoracic insufficiency syndrome (TIS) was described in 2003 as the inability of the thorax to support normal respiration or lung growth. TIS includes a broad and disparate group of typically degenerative thoracospinal conditions. Although TIS arises due to a heterogeneous group of disorders and thus its incidence is not well quantified, general approaches to management and treatment exist. Evolving imaging techniques and measurements of health-related quality of life augment tests of pulmonary function to quantify disease burden, longitudinally and pre- and post-intervention. Intervention is primarily via growth-sparing surgery, for which several device options exist, to preserve vertical growth prior to a definitive spinal fusion at skeletal maturity.

Impact of growth friendly interventions on spine and pulmonary outcomes of patients with spinal muscular atrophy.

PURPOSE: Patients with spinal muscular atrophy (SMA) are often treated with growth friendly devices such as vertical expandable prosthetic titanium rib(VEPTR) and magnetically controlled growing rods(MCGR) to correct spinal deformity and improve pulmonary function. There is limited data on this topic, and the purpose of this study was to assess the effect of these constructs and the addition of chest wall support (CWS) on spinal deformity, thorax morphology and pulmonary outcomes. METHODS: This is a retrospective analysis of prospectively collected data. We included patients with chest wall deformity and scoliosis secondary to SMA who were treated with growth friendly interventions and had two-year follow-up. Descriptive statistics and univariate analyses were performed. RESULTS: This study included 66 patients (25% MCGR, 73% VEPTR, 2% unknown). Approximately 23% of constructs included CWS. The average Cobb angle improved from 67° (SD: 27°) to 50° (SD: 26°) at 2 years in patients with CWS (p = 0.02), and from 59° (SD: 20°) to 46° (SD: 15°) at 2 years in patients without CWS (p < 0.01). Hemithorax height improved in patients treated with and without CWS (p = 0.01), but hemithorax width only improved in patients with CWS (p = 0.01). One patient with CWS and two patients without CWS required additional respiratory support at 2 years. The rates of postoperative complications were not significantly different in patients treated with and without CWS (p = 0.31). CONCLUSIONS: Growth friendly constructs improve spinal deformity and may be effective in altering the progression toward respiratory failure in patients with SMA. Patients treated with CWS have significant improvements in thorax morphology compared to patients without CWS.

A novel growth-friendly system alleviates pulmonary dysplasia in early-onset scoliosis combined with thoracic insufficiency syndrome: Radiological, pathological, and transcriptomic assessments.

Background: The posterior procedure utilizing growth-friendly techniques is the golden standard for patients with early-onset scoliosis combined with thoracic insufficiency syndrome (EOS + TIS). Pulmonary hypoplasia is the main cause of dying prematurely in the EOS + TIS. This study assessed the therapeutic impact of a novel growth-friendly system on the pulmonary development of piglet's EOS + TIS model. Methods: The animal procedure period lasts 12 weeks, of which the construction of the EOS + TIS was performed at 0-8 weeks, and implantation of a novel growth-friendly system was applied at 8-12 weeks. During the animal procedure, X-rays and CT were performed to observe scoliosis, thorax, and lungs. After 12 weeks, pathological changes in lung tissue were assessed using HE and IHC staining. RNA-seq characterized novel growth-friendly system-associated differentially expressed genes (DEGs) and validated using RT-qPCR, western blotting, and IHC. Results: Implantation of the novel growth-friendly system increased body weight, body length, and total lung volume, as well as decreased the coronal and sagittal Cobb angles for the EOS + TIS model. It also ameliorated EOS + TIS-induced thickening of the alveolar wall, increased alveolar spaces, and decreased alveolar number and diameter. In lung tissue, a total of 790 novel growth-friendly system-associated DEGs were identified, and they were mainly involved in the regulation of immune, inflammatory, calcium transport, and vascular development. Among these DEGs, BDKRB1, THBS1, DUSP1, IDO1, and SPINK5 were hub genes, and their differential expression was consistent with RNA-seq results in lung tissues. Conclusion: The novel growth-friendly system has mitigated scoliosis and pulmonary hypoplasia in the EOS + TIS model. We further elucidate the molecular mechanisms underlying the amelioration of pulmonary hypoplasia.

A porcine model of early-onset scoliosis combined with thoracic insufficiency syndrome: Construction and transcriptome analysis.

BACKGROUND: Early-onset scoliosis (EOS) is a scoliosis deformity caused by various reasons before the age of 10 years and is often combined with thoracic insufficiency syndrome (TIS) causing patients with difficulty in securing lung growth in the thoracic cage. Currently, there is a shortage of effective large animal models for evaluating EOS + TIS in therapeutic studies. Consequently, we propose to construct a porcine EOS + TIS model and evaluate its transcriptome changes by RNA sequencing. METHODS: Piglets were constructed using unilateral posterior spine-tethering and ipsilateral rib-tethering in the EOS + TIS model, and X-ray and computed tomography (CT) were performed to assess growth changes in the spine, thoracic cage and lungs. The H&E and Masson staining was performed for pathological analysis of lung tissue. After RNA sequencing of lung tissues, data were analyzed for differential expression of mRNA, functional enrichment analysis (GO, KEGG and GSEA) and protein-protein interaction (PPI) network construction, and differential expression of hub gene was verified by RT-qPCR. RESULTS: In the model group, growth (body weight and length) of piglets was significantly delayed; fusion of ribs occurred and cobb angle changes in the coronal and sagittal planes were significantly enlarged; total lung volume (TLV) was significantly reduced, especially at the T7-T10 level. Pathological analysis revealed that, in the model lung tissue, the alveolar wall of was poorly perfused, the alveolar space was enlarged, the number and size of alveoli were significantly reduced, and it was accompanied by collagen fiber deposition. Moreover, a total of 432 differentially expressed mRNAs (DE-mRNAs) were identified in model lung tissues, which contained 262 down-regulated and 170 up-regulated DE-mRNAs, and they were mainly involved in the regulation of immunity, inflammation, cell cycle and extracellular matrix. A PPI network containing 71 nodes and 158 edges was constructed based on all DE-mRNAs, and JUN, CCL2, EGR1, ATF3, BTG2, DUSP1 and THBS1 etc. were hub gene. CONCLUSIONS: Overall, we constructed a porcine model that was capable of replicating the common clinical features of EOS + TIS such as rib fusion, asymmetric thoracic cage, increased cobb angle, decreased TLV, and pulmonary hypoplasia. Also, we revealed transcriptomic changes in the EOS + TIS model that may cause pulmonary hypoplasia.

Effects of spinal deformities on lung development in children: a review.

Scoliosis before the age of 5 years is referred to as early-onset scoliosis (EOS). While causes may vary, EOS can potentially affect respiratory function and lung development as children grow. Moreover, scoliosis can lead to thoracic insufficiency syndrome when aggravated or left untreated. Therefore, spinal thoracic deformities often require intervention in early childhood, and solving these problems requires new methods that include the means for both deformity correction and growth maintenance. Therapeutic strategies for preserving the growing spine and thorax include growth rods, vertically expandable titanium artificial ribs, MAGEC rods, braces and casts. The goals of any growth-promoting surgical strategy are to alter the natural history of cardiorespiratory development, limit the progression of underlying spondylarthrosis deformities and minimize negative changes in spondylothorax biomechanics due to the instrumental action of the implant. This review further elucidates EOS in terms of its aetiology, pathogenesis, pathology and treatment.

Case report: A simple and reliable approach for progressive internal distraction of the sternum for Jeune syndrome (asphyxiating thoracic dystrophy): preliminary experience and literature review of surgical techniques.

Background: Described for the first time in 1954, Jeune syndrome (JS), often called asphyxiating thoracic dystrophy, is a congenital musculoskeletal disease characterized by short ribs, a narrow thorax, and small limbs. In this study, we analyzed and presented our preliminary experience with a device for progressive internal distraction of the sternum (PIDS) in patients with symptomatic JS. In addition, we reviewed the contemporary English literature on existing surgical techniques for treating children with congenital JS. Material and methods: A retrospective analysis of pediatric patients (<18 years old) treated for symptomatic JS at our tertiary center between 2017 and 2023 was performed. Results: We presented two patients with JS who underwent surgery using an internal sternal distractor, a Zurich II Micro Zurich Modular Distractor, placed at the corpus of the sternum among the divided halves. Conclusions: We obtained promising results regarding the safety and effectiveness of this less-invasive device for PIDS in patients with symptomatic JS. Further studies on long-term outcomes are needed to validate these findings.

Auto-segmentation of thoraco-abdominal organs in free breathing pediatric dynamic MRI.

Quantitative analysis of the dynamic properties of thoraco-abdominal organs such as lungs during respiration could lead to more accurate surgical planning for disorders such as Thoracic Insufficiency Syndrome (TIS). This analysis can be done from semi-automatic delineations of the aforesaid organs in scans of the thoraco-abdominal body region. Dynamic magnetic resonance imaging (dMRI) is a practical and preferred imaging modality for this application, although automatic segmentation of the organs in these images is very challenging. In this paper, we describe an auto-segmentation system we built and evaluated based on dMRI acquisitions from 95 healthy subjects. For the three recognition approaches, the system achieves a best average location error (LE) of about 1 voxel for the lungs. The standard deviation (SD) of LE is about 1-2 voxels. For the delineation approach, the average Dice coefficient (DC) is about 0.95 for the lungs. The standard deviation of DC is about 0.01 to 0.02 for the lungs. The system seems to be able to cope with the challenges posed by low resolution, motion blur, inadequate contrast, and image intensity non-standardness quite well. We are in the process of testing its effectiveness on TIS patient dMRI data and on other thoraco-abdominal organs including liver, kidneys, and spleen.

Update on the Diagnosis and Management of Early-onset Scoliosis.

PURPOSE OF REVIEW: In this article, we review the most recent advancements in the approaches to EOS diagnosis and assessment, surgical indications and options, and basic science innovation in the space of early-onset scoliosis research. RECENT FINDINGS: Early-onset scoliosis (EOS) covers a diverse, heterogeneous range of spinal and chest wall deformities that affect children under 10 years old. Recent efforts have sought to examine the validity and reliability of a recently developed classification system to better standardize the presentation of EOS. There has also been focused attention on developing safer, informative, and readily available imaging and clinical assessment tools, from reduced micro-dose radiographs, quantitative dynamic MRIs, and pulmonary function tests. Basic science innovation in EOS has centered on developing large animal models capable of replicating scoliotic deformity to better evaluate corrective technologies. And given the increased variety in approaches to managing EOS in recent years, there exist few clear guidelines around surgical indications across EOS etiologies. Despite this, over the past two decades, there has been a considerable shift in the spinal implant landscape toward growth-friendly instrumentation, particularly the utilization of MCGR implants. With the advent of new biological and basic science treatments and therapies extending survivorship for disease etiologies associated with EOS, the treatment for EOS has steadily evolved in recent years. With this has come a rising volume and variation in management options for EOS, as well as the need for multidisciplinary and creative approaches to treating patients with these complex and heterogeneous disorders.

QdMRI: A system for comprehensive analysis of thoracic dynamics via dynamic MRI.

Quantitative thoracic dynamic magnetic resonance imaging (QdMRI), a recently developed technique, provides a potential solution for evaluating treatment effects in thoracic insufficiency syndrome (TIS). In this paper, we integrate all related algorithms and modules during our work from the past 10 years on TIS into one system, named QdMRI, to address the following questions: (1) How to effectively acquire dynamic images? For many TIS patients, subjects are unable to cooperate with breathing instructions during image acquisition. Image acquisition can only be implemented under free-breathing conditions, and it is not feasible to use a surrogate device for tracing breathing signals. (2) How to assess the thoracic structures from the acquired image, such as lungs, left and right, separately? (3) How to depict the dynamics of thoracic structures due to respiration motion? (4) How to use the structural and functional information for the quantitative evaluation of surgical TIS treatment and for the design of the surgery plan? The QdMRI system includes 4 major modules: dynamic MRI (dMRI) acquisition, 4D image construction, image segmentation (from 4D image), and visualization of segmentation results, dynamic measurements, and comparisons of measurements from TIS patients with those from normal children. Scanning/image acquisition time for one subject is ~20 minutes, 4D image construction time is ~5 minutes, image segmentation of lungs via deep learning is 70 seconds for all time points (with the average DICE 0.96 in healthy children), and measurement computation time is 2 seconds.

Early-onset scoliosis: a narrative review.

Early-onset scoliosis (EOS) is defined as any spinal deformity that is present before 10 years old, regardless of etiology. Deformity must be evaluated based on the intercorrelation between the lungs, spine, and thorax. Curvatures of early-onset have increased risk of progression, cardiorespiratory problems, and increased morbidity and mortality. Progression of the deformity may produce thoracic insufficiency syndrome, where a distorted thorax is unable to support normal respiratory function or lung growth. Management and treatment of EOS should pursue a holistic approach in which the psychological impact and quality of life of the patient are also taken into consideration. Growth-friendly surgical techniques have not met the initial expectations of correcting scoliotic deformity, promoting thoracic growth, and improving pulmonary function.

Lung parenchymal characterization via thoracic dynamic MRI in normal children and pediatric patients with TIS.

Quantitative thoracic dynamic magnetic resonance imaging (QdMRI), a recently developed technique, provides a potential solution for evaluating treatment effects in thoracic insufficiency syndrome (TIS). In this paper, we demonstrate how lung parenchymal characteristics can be assessed via intensity properties in lung dynamic MRI, a modality suitable for use in pediatric patients. The QdMRI-based approach includes dynamic MR image acquisition, 4D image construction, image pre-processing with non-uniformity correction and intensity standardization, and lung segmentation from the 4D constructed image via a deep learning approach, as well as extraction of image parenchymal intensity properties from the segmented lungs and statistical comparisons among different clinical scenarios. We include 22 dMRI scans from 11 TIS patients (each with both pre-operative and post-operative scans) and 23 dMRI scans from healthy children. Two-sided paired t-testing is performed to compare lung intensity properties between end of expiration (EE) and end of inspiration (EI) within TIS patients (pre-operative and post-operative, separately) and normal children. We also compare the lung intensity properties at EE and EI among pre-operative TIS patients, post-operative TIS patients, and normal children. Experimental results show that lung (T2) intensity at EI is significantly lower than that at EE and lung intensity of post-operative TIS patients is significantly lower than that in pre-operative TIS patients and closer to that of normal children than to that of pre-operative TIS patients, indicating improvement in lung aeration. To our knowledge, this is the first study to provide a quantitative dynamic functional method to analyze lung parenchyma during tidal breathing on dynamic MRI in both healthy children and pediatric patients with TIS.

Thoracic Quantitative Dynamic MRI to Understand Developmental Changes in Normal Ventilatory Dynamics.

BACKGROUND: A database of normative quantitative measures of regional thoracic ventilatory dynamics, which is essential to understanding better thoracic growth and function in children, does not exist. RESEARCH QUESTION: How to quantify changes in the components of ventilatory pump dynamics during childhood via thoracic quantitative dynamic MRI (QdMRI)? STUDY DESIGN AND METHODS: Volumetric parameters were derived via 51 dynamic MRI scans for left and right lungs, hemidiaphragms, and hemichest walls during tidal breathing. Volume-based symmetry and functional coefficients were defined to compare left and right sides and to compare contributions of the hemidiaphragms and hemichest walls with tidal volumes (TVs). Statistical analyses were performed to compare volume components among four age-based groups. RESULTS: Right thoracic components were significantly larger than left thoracic components, with average ratios of 1.56 (95% CI, 1.41-1.70) for lung TV, 1.81 (95% CI, 1.60-2.03) for hemidiaphragm excursion TV, and 1.34 (95% CI, 1.21-1.47) for hemichest wall excursion TV. Right and left lung volumes at end-expiration showed, respectively, a 44% and 48% increase from group 2 (8 ≤ age < 10) to group 3 (10 ≤ age < 12). These numbers from group 3 to group 4 (12 ≤ age ≤ 14) were 24% and 28%, respectively. Right and left hemichest wall TVs exhibited, respectively, 48% and 45% increases from group 3 to group 4. INTERPRETATION: Normal right and left ventilatory volume components have considerable asymmetry in morphologic features and dynamics and change with age. Chest wall and diaphragm contributions vary in a likewise manner. Thoracic QdMRI can provide quantitative data to characterize the regional function and growth of the thorax as it relates to ventilation.

4D image construction from free-breathing MRI slice acquisitions of the thorax based on a concept of flux.

Retrospective 4D image construction from continuously acquired 2D slices is a necessary step to achieve high-quality 4D images. Self-gating methods, which extract breathing signals only from image information without any external gating technology, have much potential, such as in pediatric patients with thoracic insufficiency syndrome (TIS) who suffer from extreme malformations of the chest wall, diaphragm, and spine, leading to breathing that is very complex with lots of abnormal respiration cycles, including very deep or shallow cycles. Existing methods do not work well in this clinical scenario and most are not fully automatic, requiring some manual interactive operations. In this paper, we propose a fully automatic 4D dMRI construction method based on the concept of flux to address the 4D image construction from 2D slices of subjects with complex respiration. Firstly, we extract the breathing signal for each location based on the flux of the optical flow vector field of the body region from the image series. Then, we give a full analysis for all cycles and extract several normal ones and map them to one cosine respiration model for each location. After that, we re-sample one normal cycle from the respiration model for each location independently. All of these resampled normal cycles form the final constructed 4D image. Qualitative and quantitative evaluations on 25 subjects show that the proposed method can handle datasets from subjects with more complex respiration and achieves good self-consistency results while maintaining time and space continuity.

Long term outcome of vertical expandable prosthetic titanium rib treatment in children with early onset scoliosis.

The vertical expandable prosthetic titanium rib (VEPTR) device was originally developed for the treatment of thoracic insufficiency syndrome with the aim of improving respiratory function of affected patients. Although clinically obvious, the changes in pulmonary function of VEPTR-treated patients are difficult to assess when using common lung function tests, and newer techniques based on functional magnetic resonance imaging (MRI) are currently being evaluated. The potential of improving lung function and simultaneously controlling the spinal deformity has continuously broadened the spectrum of indications for VEPTR, not least due to the frequent reports of complications with spine-based traditional growing rods (tGR). However, the initial enthusiasm of spine-sparing deformity correction has progressively subsided with the increasing number of reports on complications, including the detection of extraspinal ossifications along the implants and across ribs. The avoidance of repetitive surgical implant lengthening with the availability of motorized distraction-based implants has further diminished the use of VEPTR, especially in the absence of volume-depletion deformities of the thorax. In view of the still scarce reporting on the ultimate strategy of VEPTR treatment and the lack of long-term follow-up of patients receiving growth-sparing surgery, only limited conclusions can be drawn so far. Based on the available reports, however, the intended deformity corrections with final fusion surgeries can be achieved to a rather limited extent, while the complication and reoperation rates are still very high.

Anesthesia for Innovative Pediatric Surgical Procedures.

Over the past few decades, there have been many advances in pediatric surgery, some using new devices (eg, VEPTR, MAGEC rods) and others using less invasive approaches (eg, Nuss procedure, endoscopic cranial suture release, minimally invasive tethered cord release). Although many of these procedures were initially met with caution or skepticism, continued experience over the past few decades has shown that these procedures are safe and effective. This article reviews the anesthetic considerations for these conditions and procedures.

Expansion Thoracoplasty as a Life-Saving Procedure in an Adolescent With Severe Spinal Deformity and Sacral Agenesis.

STUDY DESIGN: Case report. OBJECTIVES: To describe use of expansion thoracoplasty (ET) for severe thoracic insufficiency syndrome (TIS) in an adolescent with severe spinal deformity. BACKGROUND: ET is typically performed in young patients with TIS to increase chest cavity volume, improve alveolar expansion, and potentially improve alveolar proliferation. ET has not been well-described in adolescent patients with TIS. METHOD: A mature adolescent with previously treated myelokyphosis and sacral agenesis developed severe TIS with dependence on supplemental oxygen and noninvasive ventilation. She was treated with two-stage bilateral ET and vertical expandable prosthetic titanium rib (VEPTR) placement. Yearly pulmonary function testing (PFT) was performed over 7 years of follow-up. RESULTS: Significant clinical pulmonary improvement was achieved and maintained at final follow-up, as the patient no longer required supplemental oxygen. Percentage predicted forced vital capacity (FVC) improved from 29% to 36%; percentage predicted forced expiratory volume-1 second (FEV1) improved from 30% to 36%. CONCLUSIONS: This case demonstrates that improvement and stabilization of respiratory function can be achieved with instrumented ET in a skeletally mature adolescent with severe TIS and spinal deformity.

Intraspinal Anomalies in Early Onset Scoliosis: Current Concepts.

Early onset scoliosis (EOS) is deformity of the spine below the age of 5 years. Children with EOS are at risk of impaired thoracic cage development and pulmonary maturation. Initial evaluation consists of determining the etiological cause for EOS, i.e., congenital, neurogenic, idiopathic, or syndromic. The advent of magnetic resonance imaging in recent times has lead to increased awareness of neurogenic causes leading to EOS. Evaluation of spinal cord anomalies in EOS is very important as early diagnosis and treatment can help in deformity stabilization and regression. Also, any surgical or nonsurgical intervention to correct the deformity without prior treatment of spinal cord anomalies can lead to disastrous neurological complications.

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 thoraco-abdominal 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 thoraco-abdominal 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 thoraco-abdominal 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.

Clinical-pathological correlations in three patients with fibrodysplasia ossificans progressiva.

OBJECTIVE: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder in which heterotopic bone forms in the soft tissues. This often occurs in response to injury or inflammation, leading to joint immobilization and significant disability. There are currently no definitive treatment options for this devastating disease. Although the most dramatic phenotype in FOP is the episodic and progressive heterotopic ossification, patients report a number of symptoms that affect other organ systems. Post-mortem examination of FOP patients may contribute to our understanding of the underlying pathophysiology and complications of this disease. Here, we present the autopsy findings from three patients with FOP. FINDINGS: Autopsy findings in two of the three patients confirmed that the cause of death was cardiorespiratory failure in the setting of severe thoracic insufficiency from heterotopic ossification. Both of these patients also had evidence of right ventricular dilatation likely secondary to thoracic insufficiency. The third patient died from complications of a traumatic head injury after a fall but also had post-mortem evidence of thoracic insufficiency syndrome. All three patients had extensive, widespread heterotopic ossification and joint deformities consistent with FOP. There was extensive ossification of the spinal ligament in these patients, which may contribute to cervical spine rigidity. One patient was diagnosed post-mortem with a brainstem malformation. No additional significant abnormalities were noted in the other organ systems. Finally, we also demonstrate that cadaveric skin fibroblasts can be isolated for use as a potential source for future in vitro cell culture studies. CONCLUSIONS: This autopsy case series provides valuable information about the underlying complications of FOP and contributes significantly to our knowledge of this rare yet debilitating disorder. Thoracic insufficiency syndrome, right heart dysfunction, widespread heterotopic ossification, spinal ligament ossification, and CNS malformations were clearly evident; however, most other non-bone tissues appeared to be spared from gross malformations. Finally, the ability to isolate live cells from cadaveric skin is an important technique that will facilitate future studies, particularly as induced pluripotent stem cells and other cell-based technologies evolve. This case series highlights the importance of post-mortem examinations and their contribution to our current knowledge of disease pathophysiology and comorbidities.

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.