Do Rib-Based Anchors Impair Chest Wall Motion in Early Onset Scoliosis (EOS)?

Purpose: There is a concern in pediatric surgery practice that rib-based fixation may limit chest wall motion in early onset scoliosis (EOS). The purpose of this study is to address the above concern by assessing the contribution of chest wall excursion to respiration before and after surgery. Methods: Quantitative dynamic magnetic resonance imaging (QdMRI) is performed on EOS patients (before and after surgery) and normal children in this retrospective study. QdMRI is purely an image-based approach and allows free breathing image acquisition. Tidal volume parameters for chest walls (CWtv) and hemi-diaphragms (Dtv) were analyzed on concave and convex sides of the spinal curve. EOS patients (1-14 years) and normal children (5-18 years) were enrolled, with an average interval of two years for dMRI acquisition before and after surgery. Results: CWtv significantly increased after surgery in the global comparison including all EOS patients (p < 0.05). For main thoracic curve (MTC) EOS patients, CWtv significantly improved by 50.24% (concave side) and 35.17% (convex side) after age correction (p < 0.05) after surgery. The average ratio of Dtv to CWtv on the convex side in MTC EOS patients was not significantly different from that in normal children (p=0.78), although the concave side showed the difference to be significant. Conclusion: Chest wall component tidal volumes in EOS patients measured via QdMRI did not decrease after rib-based surgery, suggesting that rib-based fixation does not impair chest wall motion in pediatric patients with EOS.

Virtual Growing Child (VGC): A general normative comparative system via quantitative dynamic MRI for quantifying pediatric regional respiratory anomalies with application in thoracic insufficiency syndrome (TIS).

Background: A normative database of regional respiratory structure and function in healthy children does not exist. Methods: VGC provides a database with four categories of regional respiratory measurement parameters including morphological, architectural, dynamic, and developmental. The database has 3,820 3D segmentations (around 100,000 2D slices with segmentations). Age and gender group analysis and comparisons for healthy children were performed using those parameters via two-sided t-testing to compare mean measurements, for left and right sides at end-inspiration (EI) and end-expiration (EE), for different age and gender specific groups. We also apply VGC measurements for comparison with TIS patients via an extrapolation approach to estimate the association between measurement and age via a linear model and to predict measurements for TIS patients. Furthermore, we check the Mahalanobis distance between TIS patients and healthy children of corresponding age. Findings: The difference between male and female groups (10-12 years) behave differently from that in other age groups which is consistent with physiology/natural growth behavior related to adolescence with higher right lung and right diaphragm tidal volumes for females(p<0.05). The comparison of TIS patients before and after surgery show that the right and left components are not symmetrical, and the left side diaphragm height and tidal volume has been significantly improved after surgery (p <0.05). The left lung volume at EE, and left diaphragm height at EI of TIS patients after surgery are closer to the normal children with a significant smaller Mahalanobis distance (MD) after surgery (p<0.05). Interpretation: The VGC system can serve as a reference standard to quantify regional respiratory abnormalities on dMRI in young patients with various respiratory conditions and facilitate treatment planning and response assessment. Funding: The grant R01HL150147 from the National Institutes of Health (PI Udupa).

Interactive Segmentation of Lung Tissue and Lung Excursion in Thoracic Dynamic MRI Based on Shape-guided Convolutional Neural Networks.

Purpose: Lung tissue and lung excursion segmentation in thoracic dynamic magnetic resonance imaging (dMRI) is a critical step for quantitative analysis of thoracic structure and function in patients with respiratory disorders such as Thoracic Insufficiency Syndrome (TIS). However, the complex variability of intensity and shape of anatomical structures and the low contrast between the lung and surrounding tissue in MR images seriously hamper the accuracy and robustness of automatic segmentation methods. In this paper, we develop an interactive deep-learning based segmentation system to solve this problem. Material & Methods: Considering the significant difference in lung morphological characteristics between normal subjects and TIS subjects, we utilized two independent data sets of normal subjects and TIS subjects to train and test our model. 202 dMRI scans from 101 normal pediatric subjects and 92 dMRI scans from 46 TIS pediatric subjects were acquired for this study and were randomly divided into training, validation, and test sets by an approximate ratio of 5:1:4. First, we designed an interactive region of interest (ROI) strategy to detect the lung ROI in dMRI for accelerating the training speed and reducing the negative influence of tissue located far away from the lung on lung segmentation. Second, we utilized a modified 2D U-Net to segment the lung tissue in lung ROIs, in which the adjacent slices are utilized as the input data to take advantage of the spatial information of the lungs. Third, we extracted the lung shell from the lung segmentation results as the shape feature and inputted the lung ROIs with shape feature into another modified 2D U-Net to segment the lung excursion in dMRI. To evaluate the performance of our approach, we computed the Dice coefficient (DC) and max-mean Hausdorff distance (MM-HD) between manual and automatic segmentations. In addition, we utilized Coefficient of Variation (CV) to assess the variability of our method on repeated dMRI scans and the differences of lung tidal volumes computed from the manual and automatic segmentation results. Results: The proposed system yielded mean Dice coefficients of 0.96±0.02 and 0.89±0.05 for lung segmentation in dMRI of normal subjects and TIS subjects, respectively, demonstrating excellent agreement with manual delineation results. The Coefficient of Variation and p-values show that the estimated lung tidal volumes of our approach are statistically indistinguishable from those derived by manual segmentations. Conclusions: The proposed approach can be applied to lung tissue and lung excursion segmentation from dynamic MR images with high accuracy and efficiency. The proposed approach has the potential to be utilized in the assessment of patients with TIS via dMRI routinely.

Assessment of 3D hemi-diaphragmatic motion via free-breathing dynamic MRI in pediatric thoracic insufficiency syndrome.

Purpose: Thoracic insufficiency syndrome (TIS) affects ventilatory function due to spinal and thoracic deformities limiting lung space and diaphragmatic motion. Corrective orthopedic surgery can be used to help normalize skeletal anatomy, restoring lung space and diaphragmatic motion. This study employs free-breathing dynamic MRI (dMRI) and quantifies the 3D motion of each hemi-diaphragm surface in normal and TIS patients, and evaluates effects of surgical intervention. Materials and Methods: In a retrospective study of 149 pediatric patients with TIS and 190 healthy children, we constructed 4D images from free-breathing dMRI and manually delineated the diaphragm at end-expiration (EE) and end-inspiration (EI) time points. We automatically selected 25 points uniformly on each hemi-diaphragm surface, calculated their relative velocities between EE and EI, and derived mean velocities in 13 homologous regions for each hemi-diaphragm to provide measures of regional 3D hemi-diaphragm motion. T-testing was used to compare velocity changes before and after surgery, and to velocities in healthy controls. Results: The posterior-central region of the right hemi-diaphragm exhibited the highest average velocity post-operatively. Posterior regions showed greater velocity changes after surgery in both right and left hemi-diaphragms. Surgical reduction of thoracic Cobb angle displayed a stronger correlation with changes in diaphragm velocity than reduction in lumbar Cobb angle. Following surgery, the anterior regions of the left hemi-diaphragm tended to approach a more normal state. Conclusion: Quantification of regional motion of the 3D diaphragm surface in normal subjects and TIS patients via free-breathing dMRI is feasible. Derived measurements can be assessed in comparison to normal subjects to study TIS and the effects of surgery.

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

Purpose: Analysis of the abnormal motion of thoraco-abdominal organs in respiratory disorders such as the Thoracic Insufficiency Syndrome (TIS) and scoliosis such as adolescent idiopathic scoliosis (AIS) or early onset scoliosis (EOS) can lead to better surgical plans. We can use healthy subjects to find out the normal architecture and motion of a rib cage and associated organs and attempt to modify the patient's deformed anatomy to match to it. Dynamic magnetic resonance imaging (dMRI) is a practical and preferred imaging modality for capturing dynamic images of healthy pediatric subjects. In this paper, we propose an auto-segmentation set-up for the lungs, kidneys, liver, spleen, and thoraco-abdominal skin in these dMRI images which have their own challenges such as poor contrast, image non-standardness, and similarity in texture amongst gas, bone, and connective tissue at several inter-object interfaces. Methods: The segmentation set-up has been implemented in two steps: recognition and delineation using two deep neural network (DL) architectures (say DL-R and DL-D) for the recognition step and delineation step, respectively. The encoder-decoder framework in DL-D utilizes features at four different resolution levels to counter the challenges involved in the segmentation. We have evaluated on dMRI sagittal acquisitions of 189 (near-)normal subjects. The spatial resolution in all dMRI acquisitions is 1.46 mm in a sagittal slice and 6.00 mm between sagittal slices. We utilized images of 89 (10) subjects at end inspiration for training (validation). For testing we experimented with three scenarios: utilizing (1) the images of 90 (=189-89-10) different (remaining) subjects at end inspiration for testing, (2) the images of the aforementioned 90 subjects at end expiration for testing, and (3) the images of the aforesaid 99 (=89+10) subjects but at end expiration for testing. In some situations, we can take advantage of already available ground truth (GT) of a subject at a particular respiratory phase to automatically segment the object in the image of the same subject at a different respiratory phase and then refining the segmentation to create the final GT. We anticipate that this process of creating GT would require minimal post hoc correction. In this spirit, we conducted separate experiments where we assume to have the ground truth of the test subjects at end expiration for scenario (1), end inspiration for (2), and end inspiration for (3). Results: Amongst these three scenarios of testing, for the DL-R, we achieve a best average location error (LE) of about 1 voxel for the lungs, kidneys, and spleen and 1.5 voxels for the liver and the thoraco- abdominal skin. The standard deviation (SD) of LE is about 1 or 2 voxels. For the delineation approach, we achieve an average Dice coefficient (DC) of about 0.92 to 0.94 for the lungs, 0.82 for the kidneys, 0.90 for the liver, 0.81 for the spleen, and 0.93 for the thoraco-abdominal skin. The SD of DC is lower for the lungs, liver, and the thoraco-abdominal skin, and slightly higher for the spleen and kidneys. Conclusions: Motivated by applications in surgical planning for disorders such as TIS, AIS, and EOS, we have shown an auto-segmentation system for thoraco-abdominal organs in dMRI acquisitions. This proposed setup copes 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.

Quantifying Normal Diaphragmatic Motion and Shape and their Developmental Changes via Dynamic MRI.

Background: The diaphragm is a critical structure in respiratory function, yet in-vivo quantitative description of its motion available in the literature is limited. Research Question: How to quantitatively describe regional hemi-diaphragmatic motion and curvature via free-breathing dynamic magnetic resonance imaging (dMRI)? Study Design and Methods: In this prospective cohort study we gathered dMRI images of 177 normal children and segmented hemi-diaphragm domes in end-inspiration and end-expiration phases of the constructed 4D image. We selected 25 points uniformly located on each 3D hemi-diaphragm surface. Based on the motion and local shape of hemi-diaphragm at these points, we computed the velocities and sagittal and coronal curvatures in 13 regions on each hemi-diaphragm surface and analyzed the change in these properties with age and gender. Results: Our cohort consisted of 94 Females, 6-20 years (12.09 + 3.73), and 83 Males, 6-20 years (11.88 + 3.57). We observed velocity range: ∼2mm/s to ∼13mm/s; Curvature range -Sagittal: ∼3m -1 to ∼27m -1 ; Coronal: ∼6m -1 to ∼20m -1 . There was no significant difference in velocity between genders, although the pattern of change in velocity with age was different for the two groups. Strong correlations in velocity were observed between homologous regions of right and left hemi-diaphragms. There was no significant difference in curvatures between genders or change in curvatures with age. Interpretation: Regional motion/curvature of the 3D diaphragmatic surface can be estimated using free-breathing dynamic MRI. Our analysis sheds light on here-to-fore unknown matters such as how the pediatric 3D hemi-diaphragm motion/shape varies regionally, between right and left hemi-diaphragms, between genders, and with age.

Uncommon Causes of Interlobular Septal Thickening on CT Images and Their Distinguishing Features.

Interlobular septa thickening (ILST) is a common and easily recognized feature on computed tomography (CT) images in many lung disorders. ILST thickening can be smooth (most common), nodular, or irregular. Smooth ILST can be seen in pulmonary edema, pulmonary alveolar proteinosis, and lymphangitic spread of tumors. Nodular ILST can be seen in the lymphangitic spread of tumors, sarcoidosis, and silicosis. Irregular ILST is a finding suggestive of interstitial fibrosis, which is a common finding in fibrotic lung diseases, including sarcoidosis and usual interstitial pneumonia. Pulmonary edema and lymphangitic spread of tumors are the commonly encountered causes of ILST. It is important to narrow down the differential diagnosis as much as possible by assessing the appearance and distribution of ILST, as well as other pulmonary and extrapulmonary findings. This review will focus on the CT characterization of the secondary pulmonary lobule and ILST. Various uncommon causes of ILST will be discussed, including infections, interstitial pneumonia, depositional/infiltrative conditions, inhalational disorders, malignancies, congenital/inherited conditions, and iatrogenic causes. Awareness of the imaging appearance and various causes of ILST allows for a systematic approach, which is important for a timely diagnosis. This study highlights the importance of a structured approach to CT scan analysis that considers ILST characteristics, associated findings, and differential diagnostic considerations to facilitate accurate diagnoses.

Clinical correlates of CT imaging-derived phenotypes among lean and overweight patients with hepatic steatosis.

The objective of this study is to define CT imaging derived phenotypes for patients with hepatic steatosis, a common metabolic liver condition, and determine its association with patient data from a medical biobank. There is a need to further characterize hepatic steatosis in lean patients, as its epidemiology may differ from that in overweight patients. A deep learning method determined the spleen-hepatic attenuation difference (SHAD) in Hounsfield Units (HU) on abdominal CT scans as a quantitative measure of hepatic steatosis. The patient cohort was stratified by BMI with a threshold of 25 kg/m2 and hepatic steatosis with threshold SHAD ≥ - 1 HU or liver mean attenuation ≤ 40 HU. Patient characteristics, diagnoses, and laboratory results representing metabolism and liver function were investigated. A phenome-wide association study (PheWAS) was performed for the statistical interaction between SHAD and the binary characteristic LEAN. The cohort contained 8914 patients-lean patients with (N = 278, 3.1%) and without (N = 1867, 20.9%) steatosis, and overweight patients with (N = 1863, 20.9%) and without (N = 4906, 55.0%) steatosis. Among all lean patients, those with steatosis had increased rates of cardiovascular disease (41.7 vs 27.8%), hypertension (86.7 vs 49.8%), and type 2 diabetes mellitus (29.1 vs 15.7%) (all p < 0.0001). Ten phenotypes were significant in the PheWAS, including chronic kidney disease, renal failure, and cardiovascular disease. Hepatic steatosis was found to be associated with cardiovascular, kidney, and metabolic conditions, separate from overweight BMI.

GA-Net: A geographical attention neural network for the segmentation of body torso tissue composition.

PURPOSE: Body composition analysis (BCA) of the body torso plays a vital role in the study of physical health and pathology and provides biomarkers that facilitate the diagnosis and treatment of many diseases, such as type 2 diabetes mellitus, cardiovascular disease, obstructive sleep apnea, and osteoarthritis. In this work, we propose a body composition tissue segmentation method that can automatically delineate those key tissues, including subcutaneous adipose tissue, skeleton, skeletal muscle tissue, and visceral adipose tissue, on positron emission tomography/computed tomography scans of the body torso. METHODS: To provide appropriate and precise semantic and spatial information that is strongly related to body composition tissues for the deep neural network, first we introduce a new concept of the body area and integrate it into our proposed segmentation network called Geographical Attention Network (GA-Net). The body areas are defined following anatomical principles such that the whole body torso region is partitioned into three non-overlapping body areas. Each body composition tissue of interest is fully contained in exactly one specific minimal body area. Secondly, the proposed GA-Net has a novel dual-decoder schema that is composed of a tissue decoder and an area decoder. The tissue decoder segments the body composition tissues, while the area decoder segments the body areas as an auxiliary task. The features of body areas and body composition tissues are fused through a soft attention mechanism to gain geographical attention relevant to the body tissues. Thirdly, we propose a body composition tissue annotation approach that takes the body area labels as the region of interest, which significantly improves the reproducibility, precision, and efficiency of delineating body composition tissues. RESULTS: Our evaluations on 50 low-dose unenhanced CT images indicate that GA-Net outperforms other architectures statistically significantly based on the Dice metric. GA-Net also shows improvements for the 95% Hausdorff Distance metric in most comparisons. Notably, GA-Net exhibits more sensitivity to subtle boundary information and produces more reliable and robust predictions for such structures, which are the most challenging parts to manually mend in practice, with potentially significant time-savings in the post hoc correction of these subtle boundary placement errors. Due to the prior knowledge provided from body areas, GA-Net achieves competitive performance with less training data. Our extension of the dual-decoder schema to TransUNet and 3D U-Net demonstrates that the new schema significantly improves the performance of these classical neural networks as well. Heatmaps obtained from attention gate layers further illustrate the geographical guidance function of body areas for identifying body tissues. CONCLUSIONS: (i) Prior anatomic knowledge supplied in the form of appropriately designed anatomic container objects significantly improves the segmentation of bodily tissues. (ii) Of particular note are the improvements achieved in the delineation of subtle boundary features which otherwise would take much effort for manual correction. (iii) The method can be easily extended to existing networks to improve their accuracy for this application.

MRI-Based Radiomics Analysis of Levator Ani Muscle for Predicting Urine Incontinence after Robot-Assisted Radical Prostatectomy.

BACKGROUND: The exact role of the levator ani (LA) muscle in male continence remains unclear, and so this study aims to shed light on the topic by characterizing MRI-derived radiomic features of LA muscle and their association with postoperative incontinence in men undergoing prostatectomy. METHOD: In this retrospective study, 140 patients who underwent robot-assisted radical prostatectomy (RARP) for prostate cancer using preoperative MRI were identified. A biomarker discovery approach based on the optimal biomarker (OBM) method was used to extract features from MRI images, including morphological, intensity-based, and texture-based features of the LA muscle, along with clinical variables. Mathematical models were created using subsets of features and were evaluated based on their ability to predict continence outcomes. RESULTS: Univariate analysis showed that the best discriminators between continent and incontinent patients were patients age and features related to LA muscle texture. The proposed feature selection approach found that the best classifier used six features: age, LA muscle texture properties, and the ratio between LA size descriptors. This configuration produced a classification accuracy of 0.84 with a sensitivity of 0.90, specificity of 0.75, and an area under the ROC curve of 0.89. CONCLUSION: This study found that certain patient factors, such as increased age and specific texture properties of the LA muscle, can increase the odds of incontinence after RARP. The results showed that the proposed approach was highly effective and could distinguish and predict continents from incontinent patients with high accuracy.

A phase 1 trial of adoptive transfer of vaccine-primed autologous circulating T cells in ovarian cancer.

We have previously shown that vaccination with tumor-pulsed dendritic cells amplifies neoantigen recognition in ovarian cancer. Here, in a phase 1 clinical study ( NCT01312376 /UPCC26810) including 19 patients, we show that such responses are further reinvigorated by subsequent adoptive transfer of vaccine-primed, ex vivo-expanded autologous peripheral blood T cells. The treatment is safe, and epitope spreading with novel neopeptide reactivities was observed after cell infusion in patients who experienced clinical benefit, suggesting reinvigoration of tumor-sculpting immunity.

Periprostatic Adipose Tissue MRI Radiomics-Derived Features Associated with Clinically Significant Prostate Cancer.

Background: Altered systemic and cellular lipid metabolism plays a pivotal role in the pathogenesis of prostate cancer (PCa). In this study, we aimed to characterize T1-magnetic resonance imaging (MRI)-derived radiomic parameters of periprostatic adipose tissue (PPAT) associated with clinically significant PCa (Gleason score ≥7 [3 + 4]) in a cohort of men who underwent robot-assisted prostatectomy. Methods: Preoperative MRI scans of 98 patients were identified. The volume of interest was defined by identifying an annular shell-like region on each MRI slice to include all surgically resectable visceral adipose tissue. An optimal biomarker method was used to identify features from 7631 intensity- and texture-based properties that maximized the classification of patients into clinically significant PCa and indolent tumors at the final pathology analysis. Results: Six highest ranked optimal features were derived, which demonstrated a sensitivity, specificity, and accuracy of association with the presence of clinically significant PCa, and area under a receiver operating characteristic curve of 0.95, 0.39 0.82, and 0.82, respectively. Conclusion: A highly independent set of PPAT features derived from MRI scans that predict patients with clinically significant PCa was developed and tested. With future external validation, these features may provide a more precise scientific basis for deciding to omit biopsies in patients with borderline prostate-specific antigen kinetics and multiparametric MRI readings and help in the decision of enrolling patients into active surveillance.

Prediction of lymphoma response to CAR T cells by deep learning-based image analysis.

Clinical prognostic scoring systems have limited utility for predicting treatment outcomes in lymphomas. We therefore tested the feasibility of a deep-learning (DL)-based image analysis methodology on pre-treatment diagnostic computed tomography (dCT), low-dose CT (lCT), and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images and rule-based reasoning to predict treatment response to chimeric antigen receptor (CAR) T-cell therapy in B-cell lymphomas. Pre-treatment images of 770 lymph node lesions from 39 adult patients with B-cell lymphomas treated with CD19-directed CAR T-cells were analyzed. Transfer learning using a pre-trained neural network model, then retrained for a specific task, was used to predict lesion-level treatment responses from separate dCT, lCT, and FDG-PET images. Patient-level response analysis was performed by applying rule-based reasoning to lesion-level prediction results. Patient-level response prediction was also compared to prediction based on the international prognostic index (IPI) for diffuse large B-cell lymphoma. The average accuracy of lesion-level response prediction based on single whole dCT slice-based input was 0.82+0.05 with sensitivity 0.87+0.07, specificity 0.77+0.12, and AUC 0.91+0.03. Patient-level response prediction from dCT, using the "Majority 60%" rule, had accuracy 0.81, sensitivity 0.75, and specificity 0.88 using 12-month post-treatment patient response as the reference standard and outperformed response prediction based on IPI risk factors (accuracy 0.54, sensitivity 0.38, and specificity 0.61 (p = 0.046)). Prediction of treatment outcome in B-cell lymphomas from pre-treatment medical images using DL-based image analysis and rule-based reasoning is feasible. This approach can potentially provide clinically useful prognostic information for decision-making in advance of initiating CAR T-cell therapy.

Auto-segmentation of thoracic brachial plexuses for radiation therapy planning.

Recently, deep learning networks have achieved considerable success in segmenting organs in medical images. Several methods have used volumetric information with deep networks to achieve segmentation accuracy. However, these networks suffer from interference, risk of overfitting, and low accuracy as a result of artifacts, in the case of very challenging objects like the brachial plexuses. In this paper, to address these issues, we synergize the strengths of high-level human knowledge (i.e., natural intelligence (NI)) with deep learning (i.e., artificial intelligence (AI)) for recognition and delineation of the thoracic brachial plexuses (BPs) in computed tomography (CT) images. We formulate an anatomy-guided deep learning hybrid intelligence approach for segmenting thoracic right and left brachial plexuses consisting of 2 key stages. In the first stage (AAR-R), objects are recognized based on a previously created fuzzy anatomy model of the body region with its key organs relevant for the task at hand wherein high-level human anatomic knowledge is precisely codified. The second stage (DL-D) uses information from AAR-R to limit the search region to just where each object is most likely to reside and performs encoder-decoder delineation in slices. The proposed method is tested on a dataset that consists of 125 images of the thorax acquired for radiation therapy planning of tumors in the thorax and achieves a Dice coefficient of 0.659.

A Deep Learning Based Geographic Attention Model for Body Composition Tissue Segmentation.

Measurement of body composition, including multiple types of adipose tissue, skeletal tissue, and skeletal muscle, on computed tomography (CT) images is practical given the powerful anatomical structure visualization ability of CT, and is useful for clinical and research applications related to health care and underlying pathology. In recent years, deep learning-based methods have contributed significantly to the development of automatic body composition analysis (BCA). However, the unsatisfactory segmentation performance for indistinguishable boundaries of multiple body composition tissues and the need for large-scale datasets for training deep neural networks still need to be addressed. This paper proposes a deep learning-based approach, called Geographic Attention Network (GA-Net), for body composition tissue segmentation on body torso positron emission tomography/computed tomography (PET/CT) images which leverages the body area information. The representation ability of GA-Net is significantly enhanced with the body area information as it strongly correlates with the target body composition tissue. This method achieves precise segmentation performance for multiple body composition tissues, especially for boundaries that are hard to distinguish, and effectively reduces the data requirements for training the network. We evaluate the proposed model on a dataset that includes 50 body torso PET/CT scans for segmenting 4 key bodily tissues - subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), skeletal muscle tissue (SMT), and skeleton (Sk). Experiments show that our proposed method increases segmentation accuracy, especially with a limited training dataset, by providing geographic information of target body composition tissues.

Estimating normal metabolic activity for disease quantification via PET/CT images.

In this paper, we propose a novel pipeline for conducting disease quantification in positron emission tomography/computed tomography (PET/CT) images on anatomically pre-defined objects. The pipeline is composed of standardized uptake value (SUV) standardization, object segmentation, and disease quantification (DQ). DQ is conducted on non-linearly standardized PET images and masks of target objects derived from CT images. Total lesion burden (TLB) is quantified by estimating normal metabolic activity (TMAn) in the object and subtracting this entity from total metabolic activity (TMA) of the object, thereby measuring the overall disease quantity of the region of interest without the necessity of explicitly segmenting individual lesions. TMAn is calculated with object-specific SUV distribution models. In the modeling stage, SUV models are constructed from a set of PET/CT images obtained from normal subjects with manually delineated masks of target objects. Two ways of SUV modeling are explored, where the mean of mean values of the modeling samples is utilized as a consistent normality value in the hard strategy, and the likelihood representing normal tissue is determined from the SUV distribution (histogram) for each SUV value in the fuzzy strategy. The evaluation experiments are conducted on a separate clinical dataset of normal subjects and a phantom dataset with lesions. The ratio of absolute TLB to TMA is taken as the metric, alleviating the individual difference of volume sizes and uptake levels. The results show that the ratios in normal objects are close to 0 and the ratios for lesions approach 1, demonstrating that contributions on TLB are minimal from the normal tissue and mainly from the lesion tissue.

Mendability Index: A new metric for estimating the effort required for manually editing auto-segmentations of objects of interest.

Auto-segmentation of medical images is critical to boost precision radiology and radiation oncology efficiency, thereby improving medical quality for both health care practitioners and patients. An appropriate metric to evaluate auto-segmentation results is one of the significant tools necessary for building an effective, robust, and practical auto-segmentation technique. However, by comparing the predicted segmentation with the ground truth, currently widely-used metrics usually focus on the overlapping area (Dice Coefficient) or the most severe shifting of the boundary (Hausdorff Distance), which seem inconsistent with human reader behaviors. Human readers usually verify and correct auto-segmentation contours and then apply the modified segmentation masks to guide clinical application in diagnosis or treatment. A metric called Mendability Index (MI) is proposed to better estimate the effort required for manually editing the auto-segmentations of objects of interest in medical images so that the segmentations become acceptable for the application at hand. Considering different human behaviors for different errors, MI classifies auto-segmented errors into three types with different quantitative behaviors. The fluctuation of human subjective delineation is also considered in MI. 505 3D computed tomography (CT) auto-segmentations consisting of 6 objects from 3 institutions with the corresponding ground truth and the recorded manual mending time needed by experts are used to validate the performance of the proposed MI. The correlation between the time for editing with the segmentation metrics demonstrates that MI is generally more suitable for indicating mending efforts than Dice Coefficient or Hausdorff Distance, suggesting that MI may be an effective metric to quantify the clinical value of auto-segmentations.

Combination ATR (ceralasertib) and PARP (olaparib) Inhibitor (CAPRI) Trial in Acquired PARP Inhibitor-Resistant Homologous Recombination-Deficient Ovarian Cancer.

PURPOSE: Addition of ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) to PARP inhibitors (PARPi) overcomes PARPi resistance in high-grade serous ovarian cancer (HGSOC) cell and mouse models. We present the results of an investigator-initiated study of combination PARPi (olaparib) and ATRi (ceralasertib) in patients with acquired PARPi-resistant HGSOC. PATIENTS AND METHODS: Eligible patients had recurrent, platinum-sensitive BRCA1/2 mutated or homologous recombination (HR)-deficient (HRD) HGSOC and clinically benefited from PARPi (response by imaging/CA-125 or duration of maintenance therapy; > 12 months first-line or > 6 months ≥ second-line) before progression. No intervening chemotherapy was permitted. Patients received olaparib 300 mg twice daily and ceralasertib 160 mg daily on days 1 to 7 of a 28-day cycle. Primary objectives were safety and objective response rate (ORR). RESULTS: Thirteen patients enrolled were evaluable for safety and 12 for efficacy; 62% (n = 8) had germline BRCA1/2 mutations, 23% (n = 3) somatic BRCA1/2 mutations, and 15% (n = 2) tumors with positive HRD assay. Prior PARPi indication was treatment for recurrence (54%, n = 7), second-line maintenance (38%, n = 5) and first-line treatment with carboplatin/paclitaxel (8%, n = 1). There were 6 partial responses yielding an ORR of 50% (95% confidence interval, 0.15-0.72). Median treatment duration was 8 cycles (range 4-23+). Grade (G) 3/4 toxicities were 38% (n = 5); 15% (n = 2) G3 anemia, 23% (n = 3) G3 thrombocytopenia, 8% (n = 1) G4 neutropenia. Four patients required dose reductions. No patient discontinued treatment due to toxicity. CONCLUSIONS: Combination olaparib and ceralasertib is tolerable and shows activity in HR-deficient platinum-sensitive recurrent HGSOC that benefited and then progressed with PARPi as the penultimate regimen. These data suggest that ceralasertib resensitizes PARPi-resistant HGSOCs to olaparib, warranting further investigation.

Assessment of Regional Functional Effects of Surgical Treatment in Thoracic Insufficiency Syndrome via Dynamic Magnetic Resonance Imaging.

BACKGROUND: Quantitative regional assessment of thoracic function would enable clinicians to better understand the regional effects of therapy and the degree of deviation from normality in patients with thoracic insufficiency syndrome (TIS). The purpose of this study was to determine the regional functional effects of surgical treatment in TIS via quantitative dynamic magnetic resonance imaging (MRI) in comparison with healthy children. METHODS: Volumetric parameters were derived via 129 dynamic MRI scans from 51 normal children (November 2017 to March 2019) and 39 patients with TIS (preoperatively and postoperatively, July 2009 to May 2018) for the left and right lungs, the left and right hemi-diaphragms, and the left and right hemi-chest walls during tidal breathing. Paired t testing was performed to compare the parameters from patients with TIS preoperatively and postoperatively. Mahalanobis distances between parameters of patients with TIS and age-matched normal children were assessed to evaluate the closeness of patient lung function to normality. Linear regression functions were utilized to estimate volume deviations of patients with TIS from normality, taking into account the growth of the subjects. RESULTS: The mean Mahalanobis distances for the right hemi-diaphragm tidal volume (RDtv) were -1.32 ± 1.04 preoperatively and -0.05 ± 1.11 postoperatively (p = 0.001). Similarly, the mean Mahalanobis distances for the right lung tidal volume (RLtv) were -1.12 ± 1.04 preoperatively and -0.10 ± 1.26 postoperatively (p = 0.01). The mean Mahalanobis distances for the ratio of bilateral hemi-diaphragm tidal volume to bilateral lung tidal volume (BDtv/BLtv) were -1.68 ± 1.21 preoperatively and -0.04 ± 1.10 postoperatively (p = 0.003). Mahalanobis distances decreased after treatment, suggesting reduced deviations from normality. Regression results showed that all volumes and tidal volumes significantly increased after treatment (p < 0.001), and the tidal volume increases were significantly greater than those expected from normal growth for RDtv, RLtv, BDtv, and BLtv (p < 0.05). CONCLUSIONS: Postoperative tidal volumes of bilateral lungs and bilateral hemi-diaphragms of patients with TIS came closer to those of normal children, indicating positive treatment effects from the surgical procedure. Quantitative dynamic MRI facilitates the assessment of regional effects of a surgical procedure to treat TIS. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.