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.

Mechanical instability of veins under internal pressure

Introduction Tortuous veins are often seen in the retina,cerebrum,and human legs. Venous tortuosity may affect blood flow and the wall remodeling process,both of which are associated with venous diseases. It has been shown that tortuous or vari-

Mechanisms of rectangular groove-induced multiple-microdroplet coalescences

The mechanism of microdroplet coalescence is a fundamental issue for droplet-based microfluidics. We developed an asymmetric expansion (a rectangular groove) along one side of a microchannel to achieve multiple-microdroplet trapping, collision, and coalescence. Compared with reported symmetric expansions, this asymmetric groove could easily trap microdroplets and control two or three microdroplet coalescences precisely without a requirement for temporal and spatial synchronization. To reveal the mechanisms of multiple-droplet coalescences in a groove, we observed five different coalescence patterns under different flow conditions. Moreover, we characterized the flow behavior quantitatively by simulating the velocity vector fields in both the microdroplets and continuous phase, finding good agreement with experiments. Finally, a map of coalescence forms with different capillary numbers () and flow ratios () was obtained. The results could provide a useful guidance for the design and application of droplet-based microfluidic devices.

A primitive approach to Ou MC decrescendo phenomenon with a hands-on therapy—The relation between human bilateral symmetry and disease

The Ou MC decrescendo phenomenon (OuDP) involves the placing of the contralateral hand of the examiner on the acute abdomen of female patients (Ou MC manipulation), which results in an alleviation of pain [1]. Two front-end observations showed that placement of the contralateral hand on the acute abdomen of women alleviated pain (78 of 81 women or 96.3%), while placement of the ipsilateral hand did not (0 of 39 women or 0%). This method named as Ou MC handing remedy (HR) was used to observe the immediate and cumulative effects of OuDP on 38 cases, of which 27 were self-administered and 11 were administered by the therapist. The mean age of the patients was 55.8 years (standard deviation, 22.9 years). Five minutes after initial self-administered HR, there was pain alleviation in 14 cases and symptoms or signs beyond pain improved for another 6 cases while 7 cases unevaluated. Final results showed 9 cured, 5 with partial remission and the remaining 13 with complete remission. Five minutes after initial therapist-administered HR, pain alleviation was found with 10 cases while 1 case unevaluated. The final results showed 7 cases cured, 2 with partial remission, and 2 with complete remission. The resolution of non-infectious conditions (23/ 38) with OuDP is consistent with the restoration of normal tissue function, which seems to contribute to pain alleviation and defense against infections and tumors. Interestingly, the OuDP is capable of being invoked by either the patient or the therapist. These findings warrant further investigation.

The Preliminary Approach for the Human Cancer Regression by the Interaction between Human Bilateral Symmetrical Parts—Ou MC Decrescendo Phenomenon

Ou MC decrescendo phenomenon (OuDP) is induced by interaction between human bilateral features and has shown to alleviate or cure infectious and non-infectious diseases. The resolution of non-infectious conditions with OuDP indicates to be consistent with restoration of normal tissue function (AJEM, 2012;Proc Physiol Soc, 2014). Ou MC handing remedy (HR) was utilized to induce OuDP by applying the hand to the contralateral body. Four female patients received self-administered HR separately for their diseases: 1) uterine endometrioid carcinoma stage IIIB, 2) suspicious pancreatic cancer in stage IA with isodense pancreatic nodule, elevated CA199 and dilated tortuous main pancreatic duct, 3) uterine leiomyosarcoma stage IB, and 4) suspicious gluteal metastatic lesion of chronic myelogenous leukemia. The treatments with HR showed to suppress or ameliorate oncologic changes for these patients: 1) The uterine endometrioid carcinoma regressed from stage IIIB to IA with 5 months treatment. 2) The pancreatic isodense lesion decreased from 1.6 × 1.7 to 1.0 × 1.0 cm in size with CA199 descending from 1090.0 to 136.5 (Unit/ml) associating with the main pancreatic duct diameter decreasing from 0.39 to 0.14 cm with tortuosity disappearance after 4 months treatment. 3) The frequent profuse bleeding by uterine leiomyosarcoma prominently decreased immediately with HR and subsequent HR was also effective at minimizing heavy uterine bleeding in the 3 weeks treatment. 4) The gluteal macular lesion of the case with chronic myelogenous leukemia was eliminated with 2 weeks treatment. It reveals OuDP may normalize the tumor cells and microenvironment function, which makes tumor cells conform to the *Corresponding author. regulations with apoptosis, metastasis suppression, preventing uninhibited proliferation, minimizing angiogenesis and supervision by host immunological systems. These findings warrant further investigation.