MRI-Based Patient-Specific Left Ventricular Model to Determine the Effects of Trabeculae Carneae on the Diastolic and Systolic Functions

Introduction Trabeculae carneae are irregular structures that cover the endocardial surfaces of both ventricles of human heart and account for a significant portion of the ventricular mass.However,the role of trabeculae carneae in left ventricular(LV)function is not well understood.Previous reports suggested that trabeculae help squeeze blood from the apical region during systole[1].Our recent study suggests that trabeculae carneae hypertrophy and fibrosis contribute to increased LV stiffness in patients with diastolic heart failure,and severing free-running trabeculae carneae may improve diastolic compliance of the LV[2].Objective To understand the role of trabeculae carneae in the left ventricular diastolic and systolic functions using anatomically detailed patient-specific finite element models of the human LV.Methods(1)Image acquisition An explanted human heart was collected from a 63 year old female donor with a history of stroke and congestive heart failure within 24 hours postmortem from South Texas Blood and Tissue Center(San Antonio,TX).The heart was de-identified in accordance with Institutional Review Board(IRB)requirements and informed consent for research was obtained from the donor’s family.Three-dimensional MRI scanning was conducted on a 3T(128 MHz)MRI system(TIM Trio,Siemens Medical Solutions),comprised of a superconducting magnet with a 60 cm diameter accessible bore,when the heart was submerged in a saline filled plastic container.(2)Finite element analysis Three distinct LV models were derived from the MR images.The first model was the intact trabeculated model(TM)which contained all trabeculae carneae and papillary muscles.This high-resolution anatomically detailed 3D model of the LV was segmented from 2D MR images in DICOM format using Mimics(Materialise NV,Leuven,Belgium).The second model was the papillary model(PM),in which the papillary muscles remain intact but most of the trabeculae carneae were excluded in the smoothing process.The third model was the smooth model(SM)in which the trabeculae carneae and papillary muscles were excluded during image segmentation.Finite element(FE)models of the TM,PM and SM were created by meshing 3D reconstructions of the acquired MR images using tetrahedral elements(ICEM,Ansys Inc.,Canonsburg,PA).The mesh size was selected after a pilot study on mesh sensitivity.The passive cardiac muscle was characterized as a hyperelastic,incompressible,transversely isotropic material with a Fung exponential strain energy function.The material constants were determined by matching the end-diastolic pressure-volume relationship with the empirical Klotz relation[3].A rule-based myocardial fiber algorithm was adopted to generate the myofiber directions [4].The active contraction(i.e.,systolic contraction)was modeled by the time varying'Elastance'active contraction model.The contractile parameter Tmax was determined and calibrated so that the FE predicted ejection fraction(EF)of TM matched the EF of a normal human heart at the specified end-systolic pressure[3].The analysis of the TM,PM,and SM models were implemented using the open-source finite element package FEBio(www.febio.org).In all models,the rigid body motion was suppressed by constraining the base from moving in all directions.The end-diastolic and end-systolic pressure-volume relationships(EDPVR and ESPVR)were obtained and characterized by an exponential function and the slope,respectively.Results Our simulation results showed that independent of the material model,the EDPVR curve shifts to the right in PM and SM compared to TM.However,the ESPVR curve may shift to the right or left in PM compared to TM,while shifting tothe right in SM for all material models.EDPVR was steeper in TM compared to PM and SM;however,ESPVR was found to be steeper in PM than in TM and SM.The predicted parameters of EDPVR and ESPVR showed lower average exponential term in PM and SM compared to TM,indicating a significant improvement in the compliance and global diastolic function of less trabeculated LV models(P<0.01).Similarly,the higher average elastance EEs and lower volume intersect in PM compared to TM,suggests that mild cutting of trabeculae carneae slightly improves the global systolic function of the LV(P=0.89).However,cutting all trabeculae carneae and papillary muscles in SM had a significant adverse effect on the global systolic function(P<0.01).Discussion and conclusions Most patient-specific LV studies in the literature have used smoothed ventricular geometries.We used high resolution MRI to capture the endocardial details of the LV.Though reproducing very fine trabeculae carneae was restricted by the MRI resolution,our results demonstrated the importance of considering endocardial structures,i.e.papillary muscles and trabeculae carneae,in the assessment of LV global function in patient-specific computational LV models.The present work is consistent with the observation that diastolic performance improved after severing trabeculae carneae due to a reduction in LV stiffness[2].Furthermore,our results also suggest that severing trabeculae carneae(without affecting papillary muscle)may improve LV systolic function.Our model results are consistent with experimental measurements using ex vivo rabbit heart perfusion [5].This improvement would be greater in hypertrophic hearts because trabeculae carneae are also hypertrophic and more fibrotic.Left ventricular hypertrophy is often associated with heart failure with preserved ejection fraction(HFpEF).There is no effective treatment for HFpEF,which is characterized by impaired diastolic relaxation due to increased LV stiffness.Our results indicate that trabecular cutting could be an effective treatment for HFpEF.

Lesion-symptom mapping with NIHSS sub-scores in ischemic stroke patients

Background Lesion-symptom mapping(LSM)is a statistical technique to investigate the population-specific relationship between structural integrity and post-stroke clinical outcome.In clinical practice,patients are commonly evaluated using the National Institutes of Health Stroke Scale(NIHSS),an 11-domain clinical score to quantitate neurological deficits due to stroke.So far,LSM studies have mostly used the total NIHSS score for analysis,which might not uncover subtle structure–function relationships associated with the specific sub-domains of the NIHSS evaluation.Thus,the aim of this work was to investigate the feasibility to perform LSM analyses with sub-score information to reveal category-specific structure–function relationships that a total score may not reveal.Methods Employing a multivariate technique,LSM analyses were conducted using a sample of 180 patients with NIHSS assessment at 48-hour post-stroke from the ESCAPE trial.The NIHSS domains were grouped into six categories using two schemes.LSM was conducted for each category of the two groupings and the total NIHSS score.Results Sub-score LSMs not only identify most of the brain regions that are identified as critical by the total NIHSS score but also reveal additional brain regions critical to each function category of the NIHSS assessment without requiring extensive,specialised assessments.Conclusion These findings show that widely available sub-scores of clinical outcome assessments can be used to investigate more specific structure–function relationships,which may improve predictive modelling of stroke outcomes in the context of modern clinical stroke assessments and neuroimaging.