Binu Enchakalody

Use of Analytic Morphomics of Liver, Spleen, and Body Composition to Identify Patients at Risk for Cirrhosis

BACKGROUND & AIMS A diagnosis of cirrhosis can be made on the basis of findings from imaging studies, but these are subjective. Analytic morphomics uses computational image processing algorithms to provide precise and detailed measurements of organs and body tissues. We investigated whether morphomic parameters can be used to identify patients with cirrhosis. METHODS In a retrospective study, we performed analytic morphomics on data collected from 357 patients evaluated at the University of Michigan from 2004 to 2012 who had a liver biopsy within 6 months of a computed tomography scan for any reason. We used logistic regression with elastic net regularization and cross-validation to develop predictive models for cirrhosis, within 80% randomly selected internal training set. The other 20% data were used as internal test set to ensure that model overfitting did not occur. In validation studies, we tested the performance of our models on an external cohort of patients from a different health system. RESULTS Our predictive models, which were based on analytic morphomics and demographics (morphomics model) or analytic morphomics, demographics, and laboratory studies (full model), identified patients with cirrhosis with area under the receiver operating characteristic curve (AUROC) values of 0.91 and 0.90, respectively, compared with 0.69, 0.77, and 0.76 for aspartate aminotransferase-to-platelet ratio, Lok Score, and FIB-4, respectively, by using the same data set. In the validation set, our morphomics model identified patients who developed cirrhosis with AUROC value of 0.97, and the full model identified them with AUROC value of 0.90. CONCLUSIONS We used analytic morphomics to demonstrate that cirrhosis can be objectively quantified by using medical imaging. In a retrospective analysis of multi-protocol scans, we found that it is possible to identify patients who have cirrhosis on the basis of analyses of preexisting scans, without significant additional risk or cost.

Development of a quantitative method for the diagnosis of cirrhosis

Abstract Objective. To develop a novel non-invasive, quantitative approach utilizing computed tomography scans to predict cirrhosis. Materials and methods. A total of 105 patients (54 cirrhosis and 51 normal) who had CT scans within 6 months of a liver biopsy or were identified through a Trauma registry were included in this study. Patients were randomly divided into the training set (n = 81) and the validation set (n = 24). Each liver was segmented in a semi-automated fashion from a computed tomography scan using Mimics software. The resulting liver surfaces were saved as a stereo lithography mesh into an Oracle database, and analyzed in MATLAB® for morphological markers of cirrhosis. Results. The best predictive model for diagnosing cirrhosis consisted of liver slice-bounding box slice ratio, the dimensions of the liver bounding box, liver slice area, slice perimeter, surface volume and adjusted surface area. With this model, we calculated an area under the receiver operating characteristic curve of 0.90 for the training set, and 0.91 for the validation set. For comparison, we calculated an area under the receiver operating characteristic curve of 0.70 for our dataset when we used the lab value based aspartate aminotransferase-platelet ratio index, another reported model for predicting cirrhosis. Last, by combining the aspartate aminotransferase-platelet ratio index and our model, we obtained an area under the receiving operating characteristic of 0.95. Conclusion. This study shows “proof of concept” that quantitative image analysis of livers on computed tomography scans may be utilized to predict cirrhosis in the absence of a liver biopsy.

Novel temporalis muscle and fat pad morphomic analyses aids preoperative risk evaluation and outcome assessment in nonsyndromic craniosynostosis

Introduction Analytical morphomics is the term we created to describe an innovative, highly automated, anatomically indexed processing of 3D medical imaging data captured during the course of a patients’ preoperative CT scan. Our specific aim is to determine the efficacy of craniofacial morphomic indices (CMI) such as temporalis muscle and temporal fat pad morphometric values to predict blood transfusion requirement and hospital stay in a cohort of children with nonsyndromic craniosynostosis (NSC). Methods High-throughput, semi-automated image analysis was used to reconstruct the 3-dimensional anatomy of the temporalis muscle and temporal fat pad and to quantify CMIs. The prognostic effect of CMI on clinical outcomes were evaluated among all NSC patients and compared across various craniosynostosis subtypes using Wilcoxon nonparametric tests and Kendall’s &tgr; to determine significance. Results Using preoperative CT images, we evaluated 117 children with NSC from the University of Michigan Health System. Results demonstrate that increased temporal fat pad volume and local temporalis muscle volume are associated with better clinical outcomes in craniosynostosis patients. More specifically, temporal fat pad volume was shown to be a significant predictor of perioperative blood transfusion requirements (P = 0.0033) and increased temporal muscle volume correlated with decreased hospital stay (P = 0.016) when controlling for other covariates including age, sex, weight, and preoperative hematocrit. In addition, the same significant predictors were found when examining individual subtypes of craniosynostosis. Conclusion Our findings demonstrate that maxillofacial CT scans provide a useful quantitative index reflecting general patient health, risk stratification, and probabilities of intervention in addition to their previously established ability to determine the specific pathology of the patient. We demonstrate that temporal morphomics predict the incidence of blood transfusion, hospital stay, and serve as a proxy for fitness in patients undergoing craniosynostosis surgery.

Use of temporal morphomic indices as a clinically important variable in the diagnosis of nonsyndromic craniosynostosis.

IntroductionPreoperative computed tomography (CT) evaluation of patients with nonsyndromic craniosynostosis (NSC) has focused on the bony cranial vault while ignoring the surrounding soft tissues. In this study, we posit that novel CT-derived temporal muscle and temporal fat pad morphomics (tissue thickness, area, and volume) can be used to calculate temporal morphomic indices (TMIs), which are unique to each NSC subtype (metopic, coronal, and sagittal) and divergent from normal individuals. MethodsHigh-throughput image analysis was used to reconstruct the 3-dimensional anatomy and quantify a TMI. These steps were completed in a semiautomated method using algorithms programmed in MATLAB v13.0. Differences in TMI across various craniosynostosis subtypes were assessed using Wilcoxon nonparametric tests for both patients with NSC and a control cohort of patients with trauma. ResultsUsing preoperative CT images, we evaluated 117 children with NSC from the University of Michigan Health System and 50 age-matched control patients between 1999 and 2011. Results indicate significant differences in TMI among the normal and NSC groups, with normal patients having significantly higher TMI values than patients with metopic, sagittal, and coronal synostosis. In addition, significant differences were found to exist between each craniosynostosis category. ConclusionsPatients with craniosynostosis demonstrate diminished temporalis muscle and overlying fat pad volume and thickness compared with control patients. The unique changes in temporal morphomics presented in this article demonstrate not only that the bony calvaria is affected by craniosynostosis but also that there exist quantifiable aberrations in the temporalis muscle and temporal fat pad. The methodologies described offer a novel methodology to use pre-existing CT scans to glean additional preoperative information on the soft tissue characteristics of patients with craniosynostosis.

Novel application of human morphomics to quantify temporal soft tissues in Pierre Robin and Treacher Collins.

Introduction Pierre Robin sequence (PR) and Treacher Collins syndrome (TC) are congenital disorders associated with multiple craniofacial abnormalities. The mandibular malformations linked with these maladies are closely associated with the form and function of the temporalis muscle. Despite these associations, a paucity of research has been directed at quantifying how these malformations affect the tissues of the temporal region. In this paper, we seek to quantify differences in the temporalis muscle and the temporal fat pad using a novel CT-derived analytic program to examine craniofacial morphomic indices within these patient groups in comparison to normal age-matched controls. We posit that the temporalis muscle and temporal fat pad, like other derivatives of the first branchial arch, are hypoplastic in patients with TC and PR compared to age-matched controls. Methods High-throughput image analysis was used to reconstruct the 3-dimensional (3D) anatomy and quantify morphomic measures of the temporalis muscle and temporal fat pad in children with PR, TC, and age-matched controls. These steps were completed in a semi-automated method using algorithms programmed in MATLAB v13.0. The 3D reconstructions were analyzed in 3 children with PR (6 temporal regions), 3 children with TC (6 temporal regions), and a control group of 19 children (38 temporal regions). We also quantified the same measurements in a localized “core” sample in the area of greatest thickness, providing a more consistent sample of the tissue position. Relationships between the temporal muscle and fat pad values and craniofacial abnormality type were assessed using Wilcoxon nonparametric test using exact distribution, with a P value of less than 0.05 being deemed significant. Results The mean age of our patients was 6.0 years in PR and 4.5 years in TC cohorts. We were able to establish an automated methodology to quantify the temporalis muscle and temporal fat pad based on CT characteristics. Localized temporalis volume and localized temporalis area were significantly smaller in children with PR than in the control group. Total temporalis fat volume and localized temporalis area were significantly less in children with TC than in the control group. When compared to each other, the PR group had small morphomic values compared to TC group. Conclusions There are significant morphomic differences in the temporalis muscle and the temporal fat pad in children with either PR or TC when compared to age-matched control group which can be measured from pre-existing CT scans. Specifically, both of these test groups show decreases in the morphomic measures of the temporalis region. The quantification of these changes corroborates and objectifies the clinical findings associated with these congenital deformities while simultaneously allowing for preoperative planning. Furthermore, this finding confirms that the hypoplasia seen in these patient populations is not only hypoplasia of the mandible but also of the surrounding functional matrix, which includes the temporalis muscle and temporal fat pad.

Morphomic measurement of the temporalis muscle and zygomatic bone as novel predictors of hospital-based clinical outcomes in patients with mandible fracture

Introduction Patients with mandibular fracture often have comorbidities and concomitant injuries making the decision for when and how to operate a challenge. Physicians describe “temporalis wasting” as a finding that indicates frailty; however, this is a subjective finding without quantitative values. In this study, we demonstrate that decreased morphomic values of the temporalis muscle and zygomatic bone are an objective measure of frailty associated with increased injury-induced morbidity as well as negative impact on overall hospital-based clinical outcomes in patients with mandible fracture. Methods Computed tomographic (CT) scans from all patients with a diagnosis of a mandible fracture in the University of Michigan trauma registry and with a hospital admission were collected from the years 2004 to 2011. Automated, high-throughput CT analysis was used to reconstruct the anatomy and quantify morphomic values (temporalis volume, area and thickness, and zygomatic thickness) in these patients using MATLAB v13.0 (MathWorks Inc, Natick, MA, USA). Subsequently, a subset of 16 individuals with a Glasgow Coma Scale of 14 or 15 was analyzed to control for brain injury. Clinical data were obtained, and the association between morphomic measurements and clinical outcomes was evaluated using Pearson correlation for unadjusted analysis and multiple regression for adjusted analysis. Results The mean age of patients in the study was 47.1 years. Unadjusted analysis using Pearson correlation revealed that decreases in zygomatic bone thickness correlated strongly with increases in hospital, intensive care unit, and ventilator days (P < 0.0001, P = 0.0003, and P = 0.0017, respectively). Furthermore, we found that decreases in temporalis mean thickness correlated with increases in hospital and ventilator days (P = 0.0264 and P = 0.0306, respectively). Similarly, decreases in temporalis local mean thickness are significantly correlated with increases in hospital and ventilator days (P = 0.0232 and P = 0.0472, respectively). Conclusions Decreased thicknesses of the zygomatic bone and temporalis muscle are significantly correlated with higher hospital, ventilator, and intensive care unit days in patients with mandibular fracture receiving reconstructive operations. This morphomic methodology provides an accurate, quantitative means to evaluate craniofacial trauma patient frailty, injury, and outcomes using routinely obtained CT scans. In the future, we plan to apply this approach to determine preoperative risk stratification and assist in surgical planning.

Early Development of the Mouse Morphome.

Introduction: Analytical morphomics focuses on extracting objective and quantifiable data from clinical computed tomography (CT) scans to measure patients’ frailty. Studies are currently retrospective in nature; therefore, it would be beneficial to develop animal models for well-controlled, prospective studies. The aim of this study is to develop an in vivo microCT protocol for the longitudinal acquisition of whole-body images suitable for morphomic analyses of bone. Methods: The authors performed phantom studies on 2 microCT systems (Inveon and CT120) to study tissue radiodensity and further characterize system performance for collecting animal data. The authors also describe their design of a phantom-immobilization device using phantoms and an ovariectomized (OVX) mouse. Results: The authors discovered increased consistency along the z-axis for scans acquired on the Inveon compared with CT120, and calibration by individual slice reduces variability. Objects in the field of view had more impact on measurement acquired using the CT120 compared with the Inveon. The authors also found that using the middle 80% of slices for data analysis further decreased variability, on both systems. Moreover, bone-mineral-density calibration using the QCT Pro Mini phantom improved bone-mineral-density estimates across energy spectra, which helped confirm our technique. Comparison of weekly body weights and terminal uterine mass between sham and OVX groups validated our model. Discussion: The authors present a refined microCT protocol to collect reliable and objective data. This data will be used to establish a platform for research animal morphomics that can be used to test hypotheses developed from clinical human morphomics.

Sa1104 Quantitative Visceral Fat Findings Using Analytic Morphomics Are Associated With Future Surgical Bowel Resection in Stricturing Crohn's Disease

pies were reviewed by 1 experienced blinded radiologist and gastroenterologist, respectively. Results: CT images of 9/71 subjects were read as normal on retrospective review by a radiologist. Of the remaining 62 subjects with iCWT, 39 had biopsy from the actual site of iCWT, 14 patients had biopsy at other sites due to incidental findings during colonoscopy. Biopsy was not performed in 9 patients due to unremarkable colonoscopy. Only 20 (32%) patients who had biopsy at the site of iCWT had positive findings leading to change in management. Of these 20 patients, 6 (9.6%) were diagnosed with colon cancer and the rest had other pathologies mandating change in management. Ten of 14 patients who had biopsy at sites outside an area of iCWT had pathology (3 with carcinoma). For sub-analysis, we only included 48 patients with solitary iCWT as primary indication for colonoscopy. 14 patients were excluded due to presence of some other high risk history or CT finding (i.e. personal history of cancer or lymphadenopathy on CT). 19 (39.6%) of these 48 patients had significant colonoscopy findings leading to change in management. One patient in this subgroup was diagnosed with cancer. Colonoscopy findings leading to change in management were associated with significantly increased colon wall thickness on CT (1.17 + 0.65 cm vs. 0.81 + 0.54 cm), platelets (344.1 + 190.6 vs. 240.8 + 134.0 billion/L) and non-albumin protein (Total protein Albumin; 4.0 + 0.86 mg/dl vs. 3.46 + 0.74 mg/dl) as compared to colonoscopy findings not affecting management (Table 1). Certain CT abdomen characteristics of iCWT were significantly associated with abnormal colonoscopy findings (Table 2). Conclusion: In patients with iCWT on CT abdomen, higher platelet count and nonalbumin protein as well as imaging characteristics of iCWT are associated with significant colonoscopy findings leading to change in management. Table 1. Comparison of mean (+/SD) of various variables in iCWT patients with abnormal colonoscopy and normal colonoscopy findings.