Purpose: This study was designed to seek associations between positron emission tomography/computed tomography (PET/CT) parameters, contrast enhanced neck computed tomography (CECT) and pathological findings, and to determine the potential prognostic value of PET/CT and CECT parameters in oral cavity squamous cell carcinoma (OCSCC).
Materials and method: 36 OCSCC patients underwent staging PET/CT and 30/36 of patients had CECT. PET/CT parameters were measured for the primary tumor and the hottest involved node, including maximum, mean, and peak standardized uptake values (SUV max, SUV mean, and SUV peak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), standardized added metabolic activity (SAM), and normalized standardized added metabolic activity (N SAM). Qualitative assessment of PET/CT and CECT were also performed. Pathological outcomes included: perineural invasion, lymphovascular invasion, nodal extracapsular spread, grade, pathologic T and N stages. Multivariable logistic regression models were fit for each parameter and outcome adjusting for potentially confounding variables. Multivariable Cox proportional hazards models were used for progression free survival (PFS), locoregional recurrence free survival (LRFS), overall survival (OS) and distant metastasis free survival (DMFS).
Results: In multivariable analysis, patients with high (≥ median) tumor SUV max (OR 6.3), SUV mean (OR 6.3), MTV (OR 19.0), TLG (OR 19.0), SAM (OR 11.7) and N SAM (OR 19.0) had high pathological T-stage (T3/T4) (p < 0.05). Ring/heterogeneous pattern on CECT qualitative assessment was associated with worse DMFS and OS.
Conclusion: High PET/CT parameters were associated with pathologically advanced T stage (T3/T4). Qualitative assessment of CECT has prognostic value. PET/CT parameters did not predict clinical outcome.
Total cavopulmonary connection is the result of a series of palliative surgical repairs performed on patients with single ventricle heart defects. The resulting anatomy has complex and unsteady hemodynamics characterized by flow mixing and flow separation. Although varying degrees of flow pulsatility have been observed in vivo, non-pulsatile (time-averaged) boundary conditions have traditionally been assumed in hemodynamic modeling, and only recently have pulsatile conditions been incorporated without completely characterizing their effect or importance. In this study, 3D numerical simulations with both pulsatile and non-pulsatile boundary conditions were performed for 24 patients with different anatomies and flow boundary conditions from Georgia Tech database. Flow structures, energy dissipation rates and pressure drops were compared under rest and simulated exercise conditions. It was found that flow pulsatility is the primary factor in determining the appropriate choice of boundary conditions, whereas the anatomic configuration and cardiac output had secondary effects. Results show that the hemodynamics can be strongly influenced by the presence of pulsatile flow. However, there was a minimum pulsatility threshold, identified by defining a weighted pulsatility index (wPI), above which the influence was significant. It was shown that when wPI < 30%, the relative error in hemodynamic predictions using time-averaged boundary conditions was less than 10% compared to pulsatile simulations. In addition, when wPI < 50, the relative error was less than 20%. A correlation was introduced to relate wPI to the relative error in predicting the flow metrics with non-pulsatile flow conditions.
Background: Using a bifurcated Y-graft as the Fontan baffle is hypothesized to streamline and improve flow dynamics through the total cavopulmonary connection (TCPC). This study conducted numerical simulations to evaluate this hypothesis using postoperative data from 5 patients. Methods: Patients were imaged with cardiac magnetic resonance or computed tomography after receiving a bifurcated aorto-iliac Y-graft as their Fontan conduit. Numerical simulations were performed using in vivo flow rates, as well as 2 levels of simulated exercise. Two TCPC models were virtually created for each patient to serve as the basis for hemodynamic comparison. Comparative metrics included connection flow resistance and inferior vena caval flow distribution. Results: Results demonstrate good hemodynamic outcomes for the Y-graft options. The consistency of inferior vena caval flow distribution was improved over TCPC controls, whereas the connection resistances were generally no different from the TCPC values, except for 1 case in which there was a marked improvement under both resting and exercise conditions. Examination of the connection hemodynamics as they relate to surgical Y-graft implementation identified critical strategies and modifications that are needed to potentially realize the theoretical efficiency of such bifurcated connection designs. Conclusions: Five consecutive patients received a Y-graft connection to complete their Fontan procedure with positive hemodynamic results. Refining the surgical technique for implementation should result in further energetic improvements that may help improve long-term outcomes.
Background: Analytic methods are available to acquire extensive metabolic information in a cost-effective manner for personalized medicine, yet disease risk and diagnosis mostly rely upon individual biomarkers based on statistical principles of false discovery rate and correlation. Due to functional redundancies and multiple layers of regulation in complex biologic systems, individual biomarkers, while useful, are inherently limited in disease characterization. Data reduction and discriminant analysis tools such as principal component analysis (PCA), partial least squares (PLS), or orthogonal PLS (O-PLS) provide approaches to separate the metabolic phenotypes, but do not offer a statistical basis for selection of group-wise metabolites as contributors to metabolic phenotypes. Methods: We present a dimensionality-reduction based approach termed 'biplot correlation range (BCR)' that uses biplot correlation analysis with direct orthogonal signal correction and PLS to provide the group-wise selection of metabolic markers contributing to metabolic phenotypes. Results: Using a simulated multiple-layer system that often arises in complex biologic systems, we show the feasibility and superiority of the proposed approach in comparison of existing approaches based on false discovery rate and correlation. To demonstrate the proposed method in a real-life dataset, we used LC-MS based metabolomics to determine spectrum of metabolites present in liver mitochondria from wild-type (WT) mice and thioredoxin-2 transgenic (TG) mice. We select discriminatory variables in terms of increased score in the direction of class identity using BCR. The results show that BCR provides means to identify metabolites contributing to class separation in a manner that a statistical method by false discovery rate or statistical total correlation spectroscopy can hardly find in complex data analysis for predictive health and personalized medicine.
The ultimate goal of Fontan surgical planning is to provide additional insights into the clinical decision-making process. In its current state, surgical planning offers an accurate hemodynamic assessment of the pre-operative condition, provides anatomical constraints for potential surgical options, and produces decent post-operative predictions if boundary conditions are similar enough between the pre-operative and post-operative states. Moving forward, validation with post-operative data is a necessary step in order to assess the accuracy of surgical planning and determine which methodological improvements are needed. Future efforts to automate the surgical planning process will reduce the individual expertise needed and encourage use in the clinic by clinicians. As post-operative physiologic predictions improve, Fontan surgical planning will become an more effective tool to accurately model patient-specific hemodynamics.
Cardiovascular simulations have great potential as a clinical tool for planning and evaluating patient-specific treatment strategies for those suffering from congenital heart diseases, specifically Fontan patients. However, several bottlenecks have delayed wider deployment of the simulations for clinical use; the main obstacle is simulation cost. Currently, time-averaged clinical flow measurements are utilized as numerical boundary conditions (BCs) in order to reduce the computational power and time needed to offer surgical planning within a clinical time frame. Nevertheless, pulsatile blood flow is observed in vivo, and its significant impact on numerical simulations has been demonstrated. Therefore, it is imperative to carry out a comprehensive study analyzing the sensitivity of using time-averaged BCs. In this study, sensitivity is evaluated based on the discrepancies between hemodynamic metrics calculated using time-averaged and pulsatile BCs; smaller discrepancies indicate less sensitivity. The current study incorporates a comparison between 3D patient-specific CFD simulations using both the time-averaged and pulsatile BCs for 101 Fontan patients. The sensitivity analysis involves two clinically important hemodynamic metrics: hepatic flow distribution (HFD) and indexed power loss (iPL). Paired demographic group comparisons revealed that HFD sensitivity is significantly different between single and bilateral superior vena cava cohorts but no other demographic discrepancies were observed for HFD or iPL. Multivariate regression analyses show that the best predictors for sensitivity involve flow pulsatilities, time-averaged flow rates, and geometric characteristics of the Fontan connection. These predictors provide patient-specific guidelines to determine the effectiveness of analyzing patient-specific surgical options with time-averaged BCs within a clinical time frame.
by
Kartik S. Sundareswaran;
Christopher M. Haggerty;
Diane de Zelicourt;
Lakshmi P. Dasi;
Kerem Pekkan;
David H. Frakes;
Andrew J. Powell;
Kirk R Kanter;
Mark A. Fogel;
Ajit Yoganathan
Objective: Our objective was to analyze 3-dimensional (3D) blood flow patterns within the total cavopulmonary connection (TCPC) using in vivo phase contrast magnetic resonance imaging (PC MRI).
Methods: Sixteen single-ventricle patients were prospectively recruited at 2 leading pediatric institutions for PC MRI evaluation of their Fontan pathway. Patients were divided into 2 groups. Group 1 comprised 8 patients with an extracardiac (EC) TCPC, and group 2 comprised 8 patients with a lateral tunnel (LT) TCPC. A coronal stack of 5 to 10 contiguous PC MRI slices with 3D velocity encoding (5-9 ms resolution) was acquired and a volumetric flow field was reconstructed.
Results: Analysis revealed large vortices in LT TCPCs and helical flow structures in EC TCPCs. On average, there was no difference between LT and EC TCPCs in the proportion of inferior vena cava flow going to the left pulmonary artery (43% ± 7% vs 46% ± 5%; P = .34). However, for EC TCPCs, the presence of a caval offset was a primary determinant of inferior vena caval flow distribution to the pulmonary arteries with a significant bias to the offset side.
Conclusions: 3D flow structures within LT and EC TCPCs were reconstructed and analyzed for the first time using PC MRI. TCPC flow patterns were shown to be different, not only on the basis of LT or EC considerations, but with significant influence from the superior vena cava connection as well. This work adds to the ongoing body of research demonstrating the impact of TCPC geometry on the overall hemodynamic profile.
Total cavopulmonary connection (TCPC) hemodynamics has been hypothesized to be associated with long-term complications in single ventricle heart defect patients. Rigid wall assumption has been commonly used when evaluating TCPC hemodynamics using computational fluid dynamics (CFD) simulation. Previous study has evaluated impact of wall compliance on extra-cardiac TCPC hemodynamics using fluid-structure interaction (FSI) simulation. However, the impact of ignoring wall compliance on the presumably more compliant intra-atrial TCPC hemodynamics is not fully understood. To narrow this knowledge gap, this study aims to investigate impact of wall compliance on an intra-atrial TCPC hemodynamics. A patient-specific model of an intra-atrial TCPC is simulated with an FSI model. Patient-specific 3D TCPC anatomies were reconstructed from transverse cardiovascular magnetic resonance images. Patient-specific vessel flow rate from phase-contrast magnetic resonance imaging (MRI) at the Fontan pathway and the superior vena cava under resting condition were prescribed at the inlets. From the FSI simulation, the degree of wall deformation was compared with in vivo wall deformation from phase-contrast MRI data as validation of the FSI model. Then, TCPC flow structure, power loss and hepatic flow distribution (HFD) were compared between rigid wall and FSI simulation. There were differences in instantaneous pressure drop, power loss and HFD between rigid wall and FSI simulations, but no difference in the time-averaged quantities. The findings of this study support the use of a rigid wall assumption on evaluation of time-averaged intra-atrial TCPC hemodynamic metric under resting breath-held condition.
The Fontan procedure, although an imperfect solution for children born with a single functional ventricle, is the only reconstruction at present short of transplantation. The haemodynamics associated with the total cavopulmonary connection, the modern approach to Fontan, are severely altered from the normal biventricular circulation and may contribute to the long-term complications that are frequently noted. Through recent technological advances, spear-headed by advances in medical imaging, it is now possible to virtually model these surgical procedures and evaluate the patient-specific haemodynamics as part of the pre-operative planning process. This is a novel paradigm with the potential to revolutionise the approach to Fontan surgery, help to optimise the haemodynamic results, and improve patient outcomes. This review provides a brief overview of these methods, presents preliminary results of their clinical usage, and offers insights into its potential future directions.