The potential impact of post-COVID symptoms in the healthcare sector.

BACKGROUND: The phenomenon of post-COVID syndrome (PCS) is evolving from an abstract array of non-specific symptoms to an identifiable clinical entity of variable severity. Its frequency and persistence have implications for service delivery and workforce planning. AIMS: This study was aimed to assess the prevalence of symptoms consistent with PCS and the subjective degree of recovery in a cohort of healthcare workers, focusing on those who have returned to work. METHODS: A study population of 1176 was surveyed when attending for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody testing. Two sub-groups were identified: those with known (i.e. diagnosed on PCR testing) and assumed (i.e. antibody evidence of previous infection) SARs-CoV-2 infection, at least 12 weeks prior to the study. Each group was asked about their subjective degree of recovery and the nature of their persistent symptoms. Results were analysed via excel and SPSS. RESULTS: In total, 144 employees showed PCR evidence of previous infection, with 139 of these being infected at least 12 weeks prior to the study. Of these 139, only 19% (n = 26) reported feeling 100% recovered, and 71% reported persistent symptoms. Of those with assumed SARS-CoV-2 infection (n = 78), 32 (41%) were truly asymptomatic since the commencement of the pandemic, while 46 (59%) described symptoms suggestive of possible infection at least 12 weeks prior to the study. Of this latter group, 23% (n = 18) also reported residual symptoms. CONCLUSIONS: PCS is prevalent among this group, including those not previously diagnosed with COVID-19. Its' frequency and duration present challenges to employers with regards to the management of work availability and performance.

Prognostic gene expression signature for high-grade serous ovarian cancer.

BACKGROUND: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. PATIENTS AND METHODS: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. RESULTS: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years. CONCLUSION: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.

Correction: Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma-experience of the BriTROC consortium.

This article was originally published under a CC BY NC SA License, but has now been made available under a CC BY 4.0 License.

Effect of intra-myocardial Algisyl-LVR™ injectates on fibre structure in porcine heart failure.

Recent preclinical trials have shown that alginate injections are a promising treatment for ischemic heart disease. Although improvements in heart function and global structure have been reported following alginate implants, the underlying structure is poorly understood. Using high resolution ex vivo MRI and DT-MRI of the hearts of normal control swine (n = 8), swine with induced heart failure (n = 5), and swine with heart failure and alginate injection treatment (n = 6), we visualized and quantified the fibre distribution and implant material geometry. Our findings show that the alginate injectates form solid ellipsoids with a retention rate of 68.7% ±â€¯21.3% (mean ±â€¯SD) and a sphericity index of 0.37 ±â€¯0.03. These ellipsoidal shapes solidified predominantly at the mid-wall position with an inclination of -4.9°â€¯±â€¯31.4° relative to the local circumferential direction. Overall, the change to left ventricular wall thickness and myofiber orientation was minor and was associated with heart failure and not the presence of injectates. These results show that alginate injectates conform to the pre-existing tissue structure, likely expanding along directions of least resistance as mass is added to the injection sites. The alginate displaces the myocardial tissue predominantly in the longitudinal direction, causing minimal disruption to the surrounding myofiber orientations.

A viscoactive constitutive modeling framework with variational updates for the myocardium.

We present a constitutive modeling framework for contractile cardiac mechanics by formulating a single variational principle from which incremental stress-strain relations and kinetic rate equations for active contraction and relaxation can all be derived. The variational framework seamlessly incorporates the hyperelastic behavior of the relaxed and contracted tissue along with the rate - and length - dependent generation of contractile force. We describe a three-element, Hill-type model that unifies the active tension and active deformation approaches. As in the latter approach, we multiplicatively decompose the total deformation gradient into active and elastic parts, with the active deformation parametrizing the contractile Hill element. We adopt as internal variables the fiber, cross-fiber, and sheet normal stretch ratios. The kinetics of these internal variables are modeled via definition of a kinetic potential function derived from experimental force-velocity relations. Additionally, we account for dissipation during tissue deformation by adding a Newtonian viscous potential. To model the force activation, the kinetic equations are coupled with the calcium transient obtained from a cardiomyocyte electrophysiology model. We first analyze our model at the material point level using stress and strain versus time curves for different viscosity values. Subsequently, we couple our constitutive framework with the finite element method (FEM) and study the deformation of three-dimensional tissue slabs with varying cardiac myocyte orientation. Finally, we simulate the contraction and relaxation of an ellipsoidal left ventricular model and record common kinematic measures, such as ejection fraction, and myocardial tissue volume changes.

Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma-experience of the BriTROC consortium.

BACKGROUND: Investigating tumour evolution and acquired chemotherapy resistance requires analysis of sequential tumour material. We describe the feasibility of obtaining research biopsies in women with relapsed ovarian high-grade serous carcinoma (HGSC). METHODS: Women with relapsed ovarian HGSC underwent either image-guided biopsy or intra-operative biopsy during secondary debulking, and samples were fixed in methanol-based fixative. Tagged-amplicon sequencing was performed on biopsy DNA. RESULTS: We screened 519 patients in order to enrol 220. Two hundred and two patients underwent successful biopsy, 118 of which were image-guided. There were 22 study-related adverse events (AE) in the image-guided biopsies, all grades 1 and 2; pain was the commonest AE. There were pre-specified significant AE in 3/118 biopsies (2.5%). 87% biopsies were fit-for-purpose for genomic analyses. Median DNA yield was 2.87 µg, and was higher in biopsies utilising 14 G or 16 G needles compared to 18 G. TP53 mutations were identified in 94.4% patients. CONCLUSIONS: Obtaining tumour biopsies for research in relapsed HGSC is safe and feasible. Adverse events are rare. The large majority of biopsies yield sufficient DNA for genomic analyses-we recommend use of larger gauge needles and methanol fixation for such biopsies, as DNA yields are higher but with no increase in AEs.

Methanol-based fixation is superior to buffered formalin for next-generation sequencing of DNA from clinical cancer samples.

BACKGROUND: Next-generation sequencing (NGS) of tumour samples is a critical component of personalised cancer treatment, but it requires high-quality DNA samples. Routine neutral-buffered formalin (NBF) fixation has detrimental effects on nucleic acids, causing low yields, as well as fragmentation and DNA base changes, leading to significant artefacts. PATIENTS AND METHODS: We have carried out a detailed comparison of DNA quality from matched samples isolated from high-grade serous ovarian cancers from 16 patients fixed in methanol and NBF. These experiments use tumour fragments and mock biopsies to simulate routine practice, ensuring that results are applicable to standard clinical biopsies. RESULTS: Using matched snap-frozen tissue as gold standard comparator, we show that methanol-based fixation has significant benefits over NBF, with greater DNA yield, longer fragment size and more accurate copy-number calling using shallow whole-genome sequencing (WGS). These data also provide a new approach to understand and quantify artefactual effects of fixation using non-negative matrix factorisation to analyse mutational spectra from targeted and WGS data. CONCLUSION: We strongly recommend the adoption of methanol fixation for sample collection strategies in new clinical trials. This approach is immediately available, is logistically simple and can offer cheaper and more reliable mutation calling than traditional NBF fixation.

Regional segmentation of ventricular models to achieve repolarization dispersion in cardiac electrophysiology modeling.

The electrocardiogram (ECG) is one of the most significant outputs of a computational model of cardiac electrophysiology because it relates the numerical results to clinical data and is a universal tool for diagnosing heart diseases. One key features of the ECG is the T-wave, which is caused by longitudinal and transmural heterogeneity of the action potential duration (APD). Thus, in order to model a correct wave of repolarization, different cell properties resulting in different APDs must be assigned across the ventricular wall and longitudinally from apex to base. To achieve this requirement, a regional parametrization of the heart is necessary. We propose a robust approach to obtain the transmural and longitudinal segmentation in a general heart geometry without relying on ad hoc procedures. Our approach is based on auxiliary harmonic lifting analyses, already used in the literature to generate myocardial fiber orientations. Specifically, the solution of a sequence of Laplace boundary value problems allows parametrically controlled segmentation of both heart ventricles. The flexibility and simplicity of the proposed method is demonstrated through several representative examples, varying the locations and extents of the epicardial, midwall, and endocardial layers. Effects of the control parameters on the T-wave morphology are illustrated via computed ECGs.

Design and initial operation of a two-color soft x-ray camera system on the Compact Toroidal Hybrid experiment.

A multi-camera soft x-ray diagnostic has been developed to measure the equilibrium electron temperature profile and temperature fluctuations due to magnetohydrodynamic activity on the Compact Toroidal Hybrid experiment. The diagnostic consists of three separate cameras each employing two 20-channel diode arrays that view the same plasma region through different beryllium filter thicknesses of 1.8 µm and 3.0 µm allowing electron temperature measurements between 50 eV and 200 eV. The Compact Toroidal Hybrid is a five-field period current-carrying stellarator, in which the presence of plasma current strongly modifies the rotational transform and degree of asymmetry of the equilibrium. Details of the soft x-ray emission, effects of plasma asymmetry, and impurity line radiation on the design and measurement of the two-color diagnostic are discussed. Preliminary estimates of the temperature perturbation due to sawtooth oscillations observed in these hybrid discharges are given.

Thomson scattering diagnostic system design for the Compact Toroidal Hybrid experiment.

A new Thomson scattering system using standard commercially available components has been designed for the non-axisymmetric plasmas of the Compact Toroidal Hybrid (CTH). The beam, generated by a frequency doubled Continuum PL DLS 2 J Nd:YAG laser, is passed vertically through an entrance Brewster window and an aperturing baffle system to minimize the stray laser light that could enter the collection optics. The beam line has been designed with an 8 m propagation distance to the mid-plane of the CTH device with the beam diameter kept less than 3 mm inside the plasma volume. The beam exits the vacuum system through another Brewster window and enters a beam dump, again to minimize the stray light in the vacuum chamber. Light collection, spectral processing, and signal detection are accomplished with an f/#∼ 1 aspheric lens, a commercially available Holospec f/1.8 spectrometer, and an Andor iStar DH740-18U-C3 image intensified camera. Spectral rejection of stray laser light, if needed, can be performed with the use of an optional interference filter at the spectrometer input. The system has been developed for initial single point measurements of plasmas with core electron temperatures of approximately 20-300 eV and densities of 5 × 10(18) to 5 × 10(19) m(-3) dependent upon operational scenario.

SU-E-J-58: Patient-Specific Biomechanical Head and Neck Models for Interfraction Dose Accumulation.

PURPOSE: In this abstract, we discuss a biomechanical head and neck model that will be able to represent patient setup variations as well as physiologic changes and subsequently enable dose calculations on the deformed anatomy. METHODS: We selected Multi Pose MRI as the imaging modality to aid in model development and validation. The MRI data allowed us to build a biomechanically predictive model that will enable accurate estimation of tumor position when seeded with CT data alone. The soft tissue contrast and lack of ionizing radiation when using MRI enabled us to acquire extensive imaging datasets with a suitable variety of head pose variations. These poses were selected to encompass the clinical positioning variations so that the resulting model will accurately reflect internal organ motion and deformation. All images were acquired using an 8-channel, 1.5T research MRI system in radiology. The imaging volume extended from about T3(upper thoracic vertebrae) to the top of the head, thereby covering the entire head and neck. Model components included: muscles, skeletal bones, lymph nodes, fat tissues, and organs such as salivary glands, tendons, andligaments. At first, one MRI image dataset was selected as the reference image. The biometric properties (length, volume, mass, shape), hinge constraints of the bones, and the biomechanical properties of each of the anatomies were estimated using MRIs acquired at different head and neck poses. RESULTS: The model's ability to represent different head and neck postures can be illustrated by observing the internal tissue deformations andthe model's ability to represent different postures. CONCLUSIONS: Results show that the biomechanical model was able to simulate different poses that may be exhibited during interfraction patient setup variations and intrafraction patient motion. Future work would focus on integrating dose calculations on the deforming model and validating the model deformations.

SU-E-J-192: Static Breath-Hold MRI Based Measurement of Change in Pulmonary Function Following a Course of Radiation Therapy.

PURPOSE: Radiation Therapy (RT) induced pulmonary function change may depend on the location, underlying function of that lung prior to radiations, radiation dose/fractionation and other factors. We propose to evaluate the radiation induced pulmonary function change using static breath-hold MRI scans with vascular information and 3D deformable image registration which can provide pulmonary function relative to RT dose on a regional basis. METHODS: A MRI scan pair near the end of inhale and near the end of exhale with breath hold were acquired for one lung cancer patient before RT and 6 months after RT. The patient was treated with SBRT with 55 Gy to PTVs in the right and the left lung respectively. B-spline based vesselness preserving image registration algorithm was applied to register the MRI pair for the calculation of local lung expansion as a measurement of regional pulmonary function (PF). The PF maps before RT and after RT were then mapped to the planning CT using the same algorithm tuned for MRI-CT registration. The pulmonary function change was calculated via the PF ratio between two MRI pairs. RESULTS: Strong spatial correlation was found between the irradiated lung region and the region with greatly decreased PF. Based on dose and PFC distribution, no strong determinant factor was found for PF lost in the left lung while the right lung shows that all the lung tissue receiving dose larger than 28 Gy will have a decreased PF. CONCLUSIONS: We demonstrated a method that uses static breath-hold MRI based lung imaging to evaluate radiation induced pulmonary function change which can be applied to study the dose and the pulmonary function change in a regional basis. This work is supported by NIH grant support 1R21CA144063.

Evidence for separatrix formation and sustainment with steady inductive helicity injection.

The first sustainment of toroidal plasma current of 50 kA at up to 3 times the injected currents, added in quadrature, using steady inductive helicity injection is described. Separatrix currents-currents not linking the helicity injectors-are sustained up to 40 kA. Decreases in the n=1 toroidal mode of the poloidal magnetic field at higher current amplifications indicate more quiescent, direct toroidal current drive. Results are achieved in HIT-SI (with a spheromak of major radius 0.3 m) during deuterium operations immediately after helium operation. These results represent a breakthrough in the development of this new current drive method for magnetic confinement fusion.

Associations between leptin and adiponectin receptor upregulation, visceral obesity and tumour stage in oesophageal and junctional adenocarcinoma.

BACKGROUND: Obesity is associated with oesophageal adenocarcinoma, but mechanisms linking fat and carcinogenesis remain poorly understood. Altered circulating adipocytokines may be important. This study aimed to identify pathways through which visceral fat impacts on tumour biology. METHODS: Seventy-five patients with oesophageal adenocarcinoma underwent anthropometric and radiological assessment of obesity. Expression of leptin receptor (ObR) and adiponectin receptors 1 and 2 (AdipR1, AdipR2) was quantified by real-time reverse transcriptase-polymerase chain reaction. The human oesophageal adenocarcinoma cell line OE33 was used as the calibrator sample. RESULTS: Ninety-one per cent of tumours expressed ObR, 95 per cent expressed AdipR1 and 100 per cent expressed AdipR2. Relative expression of ObR was upregulated in 67 per cent, and AdipR1 and AdipR2 were downregulated in 55 and 68 per cent respectively, relative to the calibrator sample. Upregulated ObR and AdipR2 expression was significantly associated with anthropometric and radiological measures of obesity. Upregulated ObR was associated with advanced tumour and node category (P = 0.036 and P = 0.025 respectively), and upregulated AdipR2 with nodal involvement (P = 0.037). CONCLUSION: Obesity is associated with upregulated ObR and AdipR2 expression in oesophageal adenocarcinoma. The association of ObR and AdipR2 with tumour stage suggest that pathways involving adipocytokines affect tumour biology.

The lethal and sub-lethal consequences of entomopathogenic nematode infestation and exposure for adult pine weevils, Hylobius abietis (Coleoptera: Curculionidae).

Entomopathogenic nematodes (EPN) frequently kill their host within 1-2 days, and interest in EPN focuses mainly on their lethality. However, insects may take longer to die, or may fail to die despite being infected, but little is known about the effects of EPN infection on insects, other than death. Here we investigate both lethal and sub-lethal effects of infection by two EPN species, Steinernema carpocapsae and Heterorhabditis downesi, on adults of the large pine weevil, Hylobius abietis. Following 12h nematode-weevil contact in peat, S. carpocapsae killed a significantly higher proportion of weevils (87-93%) than H. downesi (43-57%) at all concentrations tested. Less than 10% of weevils were dead within 2 days, and weevils continued to die for up to 10 days after exposure (LT(50) of 3 days or more). In a separate experiment, live weevils dissected 6 days after a 24h exposure to nematodes on filter paper harbored encapsulated and dead nematodes, showing that weevils could defend themselves against infection. Some live weevils also harbored live nematodes 6 days after they had been removed from the nematode infested medium. Feeding by weevils was not affected by infection with, or exposure to, either species of EPN. We discuss these results in relation to the use of EPN in biological control against H. abietis.

Metabolic syndrome, central obesity and insulin resistance are associated with adverse pathological features in postmenopausal breast cancer.

AIMS: Obesity is associated with both an increased risk of postmenopausal breast cancer and increased mortality rates. The mechanism is unclear, and central (visceral) obesity, insulin resistance, altered sex steroids and altered adipokines are mooted as possible factors. These features may cluster in the so-called metabolic syndrome. The relevance of metabolic syndrome to the biology of breast cancer is unknown, and this was the focus of the present study. MATERIALS AND METHODS: All postmenopausal women with newly diagnosed breast cancer (n=105) were recruited. A detailed clinical history was carried out, as well as a body composition analysis, metabolic screen and measurement of adipokines and inflammatory markers. RESULTS: The median age was 68 years (40-94 years) and the mean body mass index was 28.3+/-5.2 kg/m2, with 87% of patients centrally obese. Metabolic syndrome was diagnosed in 39% of patients, and was significantly associated with central obesity (P<0.005) and increased inflammation, with C-reactive protein levels doubling in metabolic syndrome patients compared with non-metabolic syndrome patients (10.3 vs 5.8 mg/l; P=0.084). Patients with a later pathological stage (II-IV) were significantly more likely to be obese (P=0.007), centrally obese (P=0.009), hyperglycaemic (P=0.047) and hyperinsulinaemic (P=0.026); 51% had metabolic syndrome compared with 12% for early stage disease. Patients with node-positive disease were significantly more likely to be hyperinsulaemic (P=0.030) and have metabolic syndrome (P=0.028) than patients with node-negative disease. DISCUSSION: The data suggest that metabolic syndrome and central obesity are common in postmenopausal breast cancer patients, and that metabolic syndrome may be associated with a more aggressive tumour biology.

Simulated roots and host feeding enhance infection of subterranean insects by the entomopathogenic nematode Steinernema carpocapsae.

Steinernema carpocapsae can be effective against root-feeding insects despite its reputation as a sedentary ambusher. In pot experiments, using twigs as surrogate roots and pine weevil larvae as targets, we tested the hypothesis that roots serve as physical routeways and conduits of feeding-associated stimuli, thus enhancing the success of S. carpocapsae applied at the surface against subterranean hosts. Insect mortality was lowest (25%) in the absence of plant material, increased to 48% when twigs linked nematodes and insects, and further increased to 69% when the insects were allowed feed on the twigs. This is the first experimental support for the root-routeway hypothesis.

Single-dose adjustment versus no adjustment of warfarin in stably anticoagulated patients with an occasional international normalized ratio (INR) out of range.

BACKGROUND: Well-controlled patients on warfarin may still have occasional International Normalized Ratios (INRs) outside the therapeutic range. It is unclear whether there is any benefit of a single-dose correction in this situation. AIM: To evaluate whether patients with very stable INR results should continue with the maintenance dose of warfarin without a single-dose correction, even when the result unexpectedly is moderately below or above the therapeutic range. METHODS: A) We reviewed retrospectively 364 patients with unchanged maintenance dose for at least 6 months and an occasional INR outside the therapeutic range regarding decision on dosing and the effect on the next INR. B) We randomized 160 patients with at least 3 months of unchanged maintenance dose, an occasional INR deviating to a minimum of 1.5 or a maximum of 4.4 and unexplained or temporary, removable cause to a single-dose Change or No change. Follow-up INRs and telephone interviews were obtained after 2 weeks. RESULTS: A) Retrospectively, the proportion of follow-up INRs outside the therapeutic range was 29.9% after No change, 27.1% after Increased dose and 25.7% after Skipped/reduced dose. However, the decision on No change was mainly taken in case of minimal INR deviations. B) Forty-eight (60%) of the patients randomized to Change were within the therapeutic range at follow-up versus 45 (56%) of those with No change, odds ratio 1.17 (95% confidence interval 0.59-2.30). For baseline INRs deviating down to 1.6 or up to 3.6 (therapeutic range, INR 2.0-3.0) the 2-week INRs did not differ between the groups. CONCLUSION: Our results suggest only a small or no difference between the two managements of an occasional INR out of range in terms of the 2-week follow-up INR. In stable patients on warfarin with an occasional INR outside the therapeutic range it seems reasonable to continue with the same dose without a single-dose change and perform a repeat test in about 2 weeks. (ClinicalTrials.gov number, NCT00814177.).

Building a bioresource for esophageal research: lessons from the early experience of an academic medical center.

The establishment of biorepositories, linked to clinical and epidemiologic data, are central to the goals of personalized medicine and individualized cancer therapy. Repositories of DNA, RNA, and serum samples are valuable resources for cancer research, enabling the investigation of the underlying causes of cancer development, progression, and prognosis, as well as providing a resource for the investigation of biomarkers for early detection and prediction of response. With a greater reliance on sample-derived data for molecular-based research and clinical care, improved standards and informatics for sample procurement, storage, and analysis are necessary to maximize the value of tissue collection for research participants, investigators, and academic medical centers. We present herein the experience of an academic medical center in establishing a repository for esophageal research, with discussion of elements to be considered when establishing such a resource, from the quality assurance of samples to the organized collection and storage of associated clinical data. The development of this biorepository required significant planning to identify and consent participants by dedicated clinical and research personnel. Ensuring the quality of any biobank is of utmost importance, and one must understand the sample variability that exists during the acquisition of biospecimens. The time and type of fixative have been optimized in our unit by standard operating protocols. Methods for biomolecule extraction were tested by examining both the quality and the quantity of recovered sample. These procedures were overseen by a designated biobank manager, responsible for the acquisition of the sample from surgery, which limits variability in sample collection. Our unit also has a dedicated database manager for the maintenance of quality clinical data linked to the bioresource. The development and expansion of such repositories, at local and national levels, is required to enable leading academic medical centers and their investigators to provide optimal and molecularly guided care to their patients.

Passive ventricular mechanics modelling using MRI of structure and function.

Patients suffering from dilated cardiomyopathy or myocardial infarction can develop left ventricular (LV) diastolic impairment. The LV remodels its structure and function to adapt to pathophysiological changes in geometry and loading conditions and this remodeling process can alter the passive ventricular mechanics. In order to better understand passive ventricular mechanics, a LV finite element model was developed to incorporate physiological and mechanical information derived from in vivo magnetic resonance imaging (MRI) tissue tagging, in vivo LV cavity pressure recording and ex vivo diffusion tensor MRI (DTMRI) of a canine heart. MRI tissue tagging enables quantitative evaluation of cardiac mechanical function with high spatial and temporal resolution, whilst the direction of maximum water diffusion (the primary eigenvector) in each voxel of a DTMRI directly correlates with the myocardial fibre orientation. This model was customized to the geometry of the canine LV during diastasis by fitting the segmented epicardial and endocardial surface data from tagged MRI using nonlinear finite element fitting techniques. Myofibre orientations, extracted from DTMRI of the same heart, were incorporated into this geometric model using a free form deformation methodology. Pressure recordings, temporally synchronized to the tissue tagging MRI data, were used to simulate the LV deformation during diastole. Simulation of the diastolic LV mechanics allowed us to estimate the stiffness of the passive LV myocardium based on kinematic data obtained from tagged MRI. This integrated physiological model will allow more insight into the regional passive diastolic mechanics of the LV on an individualized basis, thereby improving our understanding of the underlying structural basis of mechanical dysfunction in pathological conditions.