Equilibrium Mechanical Properties of the Nonhuman Primate Cervix.

Cervical remodeling is critical for a healthy pregnancy. Premature tissue changes can lead to preterm birth (PTB), and the absence of remodeling can lead to post-term birth, causing significant morbidity. Comprehensive characterization of cervical material properties is necessary to uncover the mechanisms behind abnormal cervical softening. Quantifying cervical material properties during gestation is challenging in humans. Thus, a nonhuman primate (NHP) model is employed for this study. In this study, cervical tissue samples were collected from Rhesus macaques before pregnancy and at three gestational time points. Indentation and tension mechanical tests were conducted, coupled with digital image correlation (DIC), constitutive material modeling, and inverse finite element analysis (IFEA) to characterize the equilibrium material response of the macaque cervix during pregnancy. Results show, as gestation progresses: (1) the cervical fiber network becomes more extensible (nonpregnant versus pregnant locking stretch: 2.03 ± 1.09 versus 2.99 ± 1.39) and less stiff (nonpregnant versus pregnant initial stiffness: 272 ± 252 kPa versus 43 ± 43 kPa); (2) the ground substance compressibility does not change much (nonpregnant versus pregnant bulk modulus: 1.37 ± 0.82 kPa versus 2.81 ± 2.81 kPa); (3) fiber network dispersion increases, moving from aligned to randomly oriented (nonpregnant versus pregnant concentration coefficient: 1.03 ± 0.46 versus 0.50 ± 0.20); and (4) the largest change in fiber stiffness and dispersion happen during the second trimester. These results, for the first time, reveal the remodeling process of a nonhuman primate cervix and its distinct regimes throughout the entire pregnancy.

Material Properties of Nonpregnant and Pregnant Human Uterine Layers.

The uterus has critical biomechanical functions in pregnancy and undergoes dramatic material growth and remodeling from implantation to parturition. The intrinsic material properties of the human uterus and how they evolve in pregnancy are poorly understood. To address this knowledge gap and assess the heterogeneity of these tissues, the time-dependent material properties of all human uterine layers were measured with nanoindentation. The endometrium-decidua layer was found to be the least stiff, most viscous, and least permeable layer of the human uterus in nonpregnant and third-trimester pregnant tissues. In pregnancy, endometrium-decidua becomes stiffer and less viscous with no material property changes observed in the myometrium or perimetrium. Additionally, uterine material properties did not significantly differ between third-trimester pregnant tissues with and without placenta accreta. The foundational data generated by this study will facilitate the development of physiologically accurate models of the human uterus to investigate gynecologic and obstetric disorders.

Anisotropic Mechanical Properties of the Human Uterus Measured by Spherical Indentation.

The mechanical function of the uterus is critical for a successful pregnancy. During gestation, uterine tissue grows and stretches to many times its size to accommodate the growing fetus, and it is hypothesized the magnitude of uterine tissue stretch triggers the onset of contractions. To establish rigorous mechanical testing protocols for the human uterus in hopes of predicting tissue stretch during pregnancy, this study measures the anisotropic mechanical properties of the human uterus using optical coherence tomography (OCT), instrumented spherical indentation, and video extensometry. In this work, we perform spherical indentation and digital image correlation to obtain the tissue's force and deformation response to a ramp-hold loading regimen. We translate previously reported fiber architecture, measured via optical coherence tomography, into a constitutive fiber composite material model to describe the equilibrium material behavior during indentation. We use an inverse finite element method integrated with a genetic algorithm (GA) to fit the material model to our experimental data. We report the mechanical properties of human uterine specimens taken across different anatomical locations and layers from one non-pregnant (NP) and one pregnant (PG) patient; both patients had pathological uterine tissue. Compared to NP uterine tissue, PG tissue has a more dispersed fiber distribution and equivalent stiffness material parameters. In both PG and NP uterine tissue, the mechanical properties differ significantly between anatomical locations.

Dosimetric effects of jaw tracking in step-and-shoot intensity-modulated radiation therapy.

The purpose of this work was to determine the dosimetric benefit to normal tissues by tracking the multi-leaf collimator (MLC) apertures with the photon jaws in step-and-shoot intensity-modulated radiation therapy (IMRT) on the Varian 2100 platform. Radiation treatment plans for ten thoracic, three pediatric, and three head and neck cancer patients were converted to plans with the jaws tracking each segment's MLC apertures, and compared to the original plans in a commercial radiation treatment planning system (TPS). The change in normal tissue dose was evaluated in the new plan by using the parameters V5, V10, and V20 (volumes receiving 5, 10 and 20 Gy, respectively) in the cumulative dose-volume histogram for the following structures: total lung minus gross target volume, heart, esophagus, spinal cord, liver, parotids, and brainstem. To validate the accuracy of our beam model, MLC transmission was measured and compared to that predicted by the TPS. The greatest changes between the original and new plans occurred at lower dose levels. In all patients, the reduction in V20 was never more than 6.3% and was typically less than 1%; the maximum reduction in V5 was 16.7% and was typically less than 3%. The variation in normal tissue dose reduction was not predictable, and we found no clear parameters that indicated which patients would benefit most from jaw tracking. Our TPS model of MLC transmission agreed with measurements with absolute transmission differences of less than 0.1% and, thus, uncertainties in the model did not contribute significantly to the uncertainty in the dose determination. We conclude that the amount of dose reduction achieved by collimating the jaws around each MLC aperture in step-and-shoot IMRT is probably not clinically significant.

Spatial correspondence of 4D CT ventilation and SPECT pulmonary perfusion defects in patients with malignant airway stenosis.

To determine the spatial overlap agreement between four-dimensional computed tomography (4D CT) ventilation and single photon emission computed tomography (SPECT) perfusion hypo-functioning pulmonary defect regions in a patient population with malignant airway stenosis. Treatment planning 4D CT images were obtained retrospectively for ten lung cancer patients with radiographically demonstrated airway obstruction due to gross tumor volume. Each patient also received a SPECT perfusion study within one week of the planning 4D CT, and prior to the initiation of treatment. Deformable image registration was used to map corresponding lung tissue elements between the extreme component phase images, from which quantitative three-dimensional (3D) images representing the local pulmonary specific ventilation were constructed. Semi-automated segmentation of the percentile perfusion distribution was performed to identify regional defects distal to the known obstructing lesion. Semi-automated segmentation was similarly performed by multiple observers to delineate corresponding defect regions depicted on 4D CT ventilation. Normalized Dice similarity coefficient (NDSC) indices were determined for each observer between SPECT perfusion and 4D CT ventilation defect regions to assess spatial overlap agreement. Tidal volumes determined from 4D CT ventilation were evaluated versus measurements obtained from lung parenchyma segmentation. Linear regression resulted in a linear fit with slope = 1.01 (R² = 0.99). Respective values for the average DSC, NDSC(1 mm) and NDSC(2 mm) for all cases and multiple observers were 0.78, 0.88 and 0.99, indicating that, on average, spatial overlap agreement between ventilation and perfusion defect regions was comparable to the threshold for agreement within 1-2 mm uncertainty. Corresponding coefficients of variation for all metrics were similarly in the range: 0.10%-19%. This study is the first to quantitatively assess 3D spatial overlap agreement between clinically acquired SPECT perfusion and specific ventilation from 4D CT. Results suggest high correlation between methods within the sub-population of lung cancer patients with malignant airway stenosis.