Effect Of Tissue Heterogeneity Research Articles

In vivo optimization of the experimental conditions for the non-invasive optical assessment of breast density

In this study, time domain diffuse optical spectroscopy is performed in the range 600–1100 nm on 11 healthy volunteers with a portable system for the quantitative characterization of breast tissue in terms of optical properties and optically-derived blood parameters, tissue constituent concentrations, and scattering parameters. A measurement protocol involving different geometries (reflectance and transmittance), subject’s positions (sitting and lying down), probing locations (outer, lower, and inner breast quadrants), and source-detector distances (2 and 3 cm) allowed us to investigate the effect of tissue heterogeneity and different measurement configurations on the results with the aim of identifying the best experimental conditions for the estimate of breast density (i.e., amount of fibro-glandular tissue in the breast) as a strong independent risk factor for breast cancer. Transmittance results, that in previous studies correlated strongly with mammographic density, are used as a reference for the initial test of the simpler and more comfortable reflectance measurement configuration. The higher source-detector distance, which probes deeper tissue, retrieves optical outcomes in agreement with higher average density tissue. Similarly, results on the outer quadrants indicate higher density than internal quadrants. These findings are coherent with breast anatomy since the concentration of dense fibro-glandular stroma is higher in deep tissue and towards the external portion of the breast, where the mammary gland is located. The dataset generated with this laboratory campaign is used to device an optimal measurement protocol for a future clinical trial, where optical results will be correlated with conventional mammographic density, allowing us to identify a subset of wavelengths and measurement configurations for an effective estimate of breast density. The final objective is the design of a simplified, compact and cost-effective optical device for a non-invasive, routine assessment of density-associated breast cancer risk.

Assessing Heterogeneity Effects on Points A, B, and Organs at Risk Doses in High-dose-Rate Brachytherapy for Cervical Cancer - A Comparison of 192Ir and 60Co Sources Using Monte Carlo N-Particle 5.

The present article deals with investigating the effects of tissue heterogeneity consideration on the dose distribution of 192Ir and 60Co sources in high-dose-rate brachytherapy (HDR-BT). A Monte Carlo N-Particle 5 (MCNP5) code was developed for the simulation of the dose distribution in homogeneous and heterogeneous phantoms for cervical cancer patients. The phantoms represented water-equivalent and human body-equivalent tissues. Treatment data for a patient undergoing HDR-BT with a 192Ir source were used as a reference for validation, and for 60Co, AAPM Task Group 43 methodology was also applied. The dose values were calculated for both source types in the phantoms. The results showed a good agreement between the calculated dose in the homogeneous phantom and the real patient's treatment data, with a relative difference of less than 5% for both sources. However, when comparing the absorbed doses at critical points such as Point A right, Point A left, Point B right, Point B left, bladder International Commission on Radiation Units and Measurement (ICRU) point, and recto-vaginal ICRU point, the study revealed significant percentage differences (approximately 5.85% to 12.02%) between the homogeneous and heterogeneous setups for both 192Ir and 60Co sources. The analysis of dose-volume histograms (DVH) indicated that organs at risk, notably the rectum and bladder, still received doses within recommended limits. The study concludes that 60Co and 192Ir sources can be effectively used in HDR-BT, provided that careful consideration is given to tissue heterogeneity effects during treatment planning to ensure optimal therapeutic outcomes.

A novel investigational preclinical model to assess fluence rate for dental oral craniofacial tissues

ObjectivePhotodynamic Therapy (PDT) and Photobiomodulation (PBM) are recognized for their potential in treating head and neck conditions. The heterogeneity of human tissue optical properties presents a challenge for effective dosimetry. The porcine mandible cadaver serves as an excellent model and has several similarities to human tissues of the dental oral craniofacial complex. This study aims to validate a novel modeling system that will help refine PDT and PBM dosimetry for the head and neck region. Methods and MaterialsLight transmission was analyzed through several tissue combinations at distances of 2 mm to 10 mm. Maximum light fluence rates (mW/cm2) were compared across tissue types to reveal the effects of tissue heterogeneity. ResultsThe study revealed that light fluence is affected by tissue composition, with dentin/enamel showing reduced transmission and soft tissue regions exhibiting elevated values. The porcine model has proven to be efficient in mimicking human tissue responses to light, enabling the potential to optimize future protocols. ConclusionThe porcine mandible cadaver is a novel model to understand the complex interactions between light and tissue. This study provides a foundation for future investigations into dosimetry optimization for PDT and PBM.

Independent Monte Carlo dose calculation identifies single isocenter multi-target radiosurgery targets most likely to fail pre-treatment measurement.

For individual targets of single isocenter multi-target (SIMT) Stereotactic radiosurgery (SRS), we assess dose difference between the treatment planning system (TPS) and independent Monte Carlo (MC), and demonstrate persistence into the pre-treatment Quality Assurance (QA) measurement. Treatment plans from 31 SIMT SRS patients were recalculated in a series of scenarios designed to investigate sources of discrepancy between TPS and independent MC. Targets with>5% discrepancy in DMean[Gy] after progressing through all scenarios were measured with SRS MapCHECK. A matched pair analysis was performed comparing SRS MapCHECK results for these targets with matched targets having similar characteristics (volume & distance from isocenter) but no such MC dose discrepancy. Of 217 targets analyzed, individual target mean dose (DMean[Gy]) fell outside a 5% threshold for 28 and 24 targets before and after removing tissue heterogeneity effects, respectively, while only 5 exceeded the threshold after removing effect of patient geometry (via calculation on StereoPHAN geometry). Significant factors affecting agreement between the TPS and MC included target distance from isocenter (0.83% decrease in DMean[Gy] per 2cm), volume (0.15% increase per cc), and degree of plan modulation (0.37% increase per 0.01 increase in modulation complexity score). SRS MapCHECK measurement had better agreement with MC than with TPS (2%/1mm / 10% threshold gamma pass rate (GPR)=99.4±1.9%vs. 93.1±13.9%, respectively). In the matched pair analysis, targets exceeding 5% for MC versus TPS also had larger discrepancies between TPS and measurement with no GPR (2%/1mm / 10% threshold) exceeding 90% (71.5%±16.1%); whereas GPR was high for matched targets with no such MC versus TPS difference (96.5%±3.3%, p=0.01). Independent MC complements pre-treatment QA measurement for SIMT SRS by identifying problematic individual targets prior to pre-treatment measurement, thus enabling plan modifications earlier in the planning process and guiding selection of targets for pre-treatment QA measurement.

Effects of tissue heterogeneity and comparisons of collapsed cone and Monte Carlo fast neutron patient dosimetry using the University of Washington clinical neutron therapy system (CNTS)

Fast neutron therapy is a high linear energy transfer (LET) radiation treatment modality offering advantages over low LET radiations. Multileaf collimator technology reduces normal-tissue dose (toxicity) and makes neutron therapy more comparable to MV x-ray treatments. Published clinical-trial and other experiences with fast neutron therapy are reported. Early comparative studies failed to consider differences in target-dose spatial conformality between x-ray and neutron treatments, which is especially important for organs-at-risk close to tumor targets. Treatments planning systems (TPS) for high-energy neutrons lag behind TPS tools for MV x-rays, creating challenges for comparative studies of clinical outcomes. A previously published Monte Carlo model of the University of Washington (UW) Clinical Neutron Therapy System (CNTS) is refined and integrated with the RayStation TPS as an external dose planning/verification tool. The collapsed cone (CC) dose calculations in the TPS are based on measured dose profiles and output factors in water, with the absolute dose determined using a tissue-equivalent ionization chamber. For comparison, independent (external) Monte Carlo simulation computes dose on a voxel-by-voxel basis using an atlas that maps Hounsfield Unit (HU) numbers to elemental composition and density. Although the CC algorithm in the TPS accurately computes neutron dose to water compared to Monte Carlo calculations, calculated dose to water differs from bone or tissue depending largely on hydrogen content. Therefore, the elemental composition of tissue and bone, rather than the material or electron density, affects fast neutron dose. While the CC algorithm suffices for reproducible patient dosimetry in fast neutron therapy, adopting methods that consider tissue heterogeneity would enhance patient-specific neutron dose accuracy relative to national standards for other types of ionizing radiation. Corrections for tissue composition have a significant impact on absolute dose and the relative biological effectiveness (RBE) of neutron treatments compared to other radiation types (MV x-rays, protons, and carbon ions).

SPECKLE IMAGES OF THE VESSELS AND HYDRODYNAMIC PHANTOMS IN OPTICAL COHERENCE TOMOGRAPHY

The results of a study of a series of sequential images of a vessel and a hydrodynamic phantom of biological tissues obtained using a Spectral Domain Optical Coherence Tomography (SP OCT) are presented. Acquired data were processed and histograms of speckle distributions were created. They demonstrated differences in the intensity distribution for three different areas of the OCT image: (1) free space, (2) wall of the vessel, and (3) the flow of scatterers. Using an optimization algorithm the histograms were approximated by various distribution functions, best result was demonstrated by the beta distribution with the determination coefficient R2 ~ 0.95. The resulting distributions quantitatively demonstrate effect of tissue heterogeneity. They show significant differences in the values of the shape and scale parameters, corresponding to the obtained beta distribution parameters, which were α ~ 1.7, β ~ 20.5 for free space, α ~ 3.1, β ~ 5.5 for the wall region of the phantom, α ~ 2.6, β ~ 1.7 for the flow of the scattering liquid. Variance matrices of the OCT images, which show correlation of speckles between adjacent pixels and those of the successive images were also obtained. Brighter areas of the variance matrix indicate a dynamic speckle structure in OCT images, while low brightness of the areas indicates static speckle structure, on the contrary.

Single-cell ATAC sequencing illuminates the cis-regulatory differentiation of taxol biosynthesis between leaf mesophyll and leaf epidermal cells in Taxus mairei

Taxol is a widely used anticancer drug; however, its accumulation pattern can vary largely among leaf tissues. Taxol biosynthesis is driven by a series of transcription factors (TFs), but the extent of chromatin changes that functionally regulate gene expression associated with taxol biosynthesis remain poorly understood. To assess the effects of tissue heterogeneity on taxol biosynthesis, we applied single-cell transposase-accessible chromatin sequencing to Taxus mairei leaves and identified differentially accessible regions. We captured 9488 independent cells with 42,192 fragment reads per cell. In total, 66.64% were confidently mapped onto the T. mairei genome. Projection analysis divided all the cells into nine clusters, which suggests a high degree of cell heterogeneity in T. mairei leaves. Based on the cell type markers, Clusters 2 and 7 were annotated as leaf mesophyll cells, and Clusters 5 and 6 were annotated as leaf epidermal cells. A differential accessibility analysis identified 9600 and 8538 leaf mesophyll and epidermal, respectively, cell-specific open chromatin regions. We predicted the genomic features of the genes involved in different stages of taxol biosynthesis, and there was a close correlation between chromatin open peaks and the expression levels of several taxol biosynthesis-related genes. We further identified a number of cell type-specific TF motifs and reference TFs that appeared to be involved in taxol biosynthesis. The study of T. mairei leaves at a single-cell resolution provides a valuable resource for determining the basic principles of the cell type-specific regulation of taxol biosynthesis.

Fast D M,M calculation in LDR brachytherapy using deep learning methods

Objective. The Monte Carlo (MC) method provides a complete solution to the tissue heterogeneity effects in low-energy low-dose rate (LDR) brachytherapy. However, long computation times limit the clinical implementation of MC-based treatment planning solutions. This work aims to apply deep learning (DL) methods, specifically a model trained with MC simulations, to predict accurate dose to medium in medium (D M,M) distributions in LDR prostate brachytherapy. Approach. To train the DL model, 2369 single-seed configurations, corresponding to 44 prostate patient plans, were used. These patients underwent LDR brachytherapy treatments in which 125I SelectSeed sources were implanted. For each seed configuration, the patient geometry, the MC dose volume and the single-seed plan volume were used to train a 3D Unet convolutional neural network. Previous knowledge was included in the network as an r 2 kernel related to the first-order dose dependency in brachytherapy. MC and DL dose distributions were compared through the dose maps, isodose lines, and dose-volume histograms. Features enclosed in the model were visualized. Main results. Model features started from the symmetrical kernel and finalized with an anisotropic representation that considered the patient organs and their interfaces, the source position, and the low- and high-dose regions. For a full prostate patient, small differences were seen below the 20% isodose line. When comparing DL-based and MC-based calculations, the predicted CTV D 90 metric had an average difference of −0.1%. Average differences for OARs were −1.3%, 0.07%, and 4.9% for the rectum D 2cc, the bladder D 2cc, and the urethra D 0.1cc. The model took 1.8 ms to predict a complete 3D D M,M volume (1.18 M voxels). Significance. The proposed DL model stands for a simple and fast engine which includes prior physics knowledge of the problem. Such an engine considers the anisotropy of a brachytherapy source and the patient tissue composition.

Homogenisation for the monodomain model in the presence of microscopic fibrotic structures

Computational models in cardiac electrophysiology are notorious for long runtimes, restricting the numbers of nodes and mesh elements in the numerical discretisations used for their solution. This makes it particularly challenging to incorporate structural heterogeneities on small spatial scales, preventing a full understanding of the critical arrhythmogenic effects of conditions such as cardiac fibrosis. In this work, we explore the technique of homogenisation by volume averaging for the inclusion of non-conductive micro-structures into larger-scale cardiac meshes with minor computational overhead. Importantly, our approach is not restricted to periodic patterns, enabling homogenised models to represent, for example, the intricate patterns of collagen deposition present in different types of fibrosis. We first highlight the importance of appropriate boundary condition choice for the closure problems that define the parameters of homogenised models. Then, we demonstrate the technique’s ability to correctly upscale the effects of fibrotic patterns with a spatial resolution of 10µm into much larger numerical mesh sizes of 100-250µm. The homogenised models using these coarser meshes correctly predict critical pro-arrhythmic effects of fibrosis, including slowed conduction, source/sink mismatch, and stabilisation of re-entrant activation patterns. As such, this approach to homogenisation represents a significant step towards whole organ simulations that unravel the effects of microscopic cardiac tissue heterogeneities.

Effects of tissue heterogeneity on trabecular micromechanics examined by microCT-based finite element analysis and digital volume correlation

Trabecular bone is natural material with heterogeneous tissue properties. The effect of tissue heterogeneity on the micromechanical behavior of trabecular bone is commonly evaluated by microCT-based finite element (microFE) analysis. Results from prior work remain inconclusive and lack of experimental validation. To address these issues, we combined microFE analysis with mechanical testing and microCT-based digital volume correlation (DVC), as a validation for the microFE approach. Porcine trabecular specimens were tested in compression as sequential microCT scans were taken. DVC was performed to extract “realistic” boundary conditions that were applied to microFE models, and to measure microstructural deformation and strain of the trabecular specimens. Heterogeneous and homogeneous microFE models of each trabecular specimen were created and compared with the experimentally measured microstructural displacement and strains. Results showed strong correlations between DVC-measured and microFE-predicted trabecular displacement and strain fields (R2 ​> ​0.9, p ​< ​0.05), regardless of heterogeneous or homogeneous material assignments. The heterogeneous and homogeneous models predicted similar magnitudes for maximum or minimum principal strains (R2 ​= ​1, p ​< ​0.05). However, incorporation of tissue heterogeneity decreased more than 16.5% in the overall stress level of the trabecular tissues. Regardless, very strong correlations were found between the heterogeneous and homogeneous model-predicted principal strains or stresses. These results together suggest that tissue heterogeneity may have little effect on microFE modeling of typical elastic displacement and strains in the trabecular bone, suggesting that homogeneous material models might be sufficient to predict general trabecular micromechanics.

The regulatory landscape of Arabidopsis thaliana roots at single-cell resolution

The scarcity of accessible sites that are dynamic or cell type-specific in plants may be due in part to tissue heterogeneity in bulk studies. To assess the effects of tissue heterogeneity, we apply single-cell ATAC-seq to Arabidopsis thaliana roots and identify thousands of differentially accessible sites, sufficient to resolve all major cell types of the root. We find that the entirety of a cell’s regulatory landscape and its transcriptome independently capture cell type identity. We leverage this shared information on cell identity to integrate accessibility and transcriptome data to characterize developmental progression, endoreduplication and cell division. We further use the combined data to characterize cell type-specific motif enrichments of transcription factor families and link the expression of family members to changing accessibility at specific loci, resolving direct and indirect effects that shape expression. Our approach provides an analytical framework to infer the gene regulatory networks that execute plant development.

Dosimetric effects of composition, location and size of tissue heterogeneities on 252Cf neutron brachytherapy

The purpose of this study is to evaluate the effect of tissue heterogeneities on dose distribution in Californium-252 (252Cf) neutron brachytherapy. The effect of location and size of heterogeneity on dose distribution was also evaluated. Neutron and photon dose rate distributions were determined in a water phantom in presence of air, lung, soft tissue and bone heterogeneities using MCNPX code. To benchmark the Monte Carlo simulation of the 252Cf source, air kerma strength (SKN), dose rate constant (ɅN) and radial dose function (gN(r)) were calculated and compared with previously reported data. Results showed a considerable reduction of neutron dose rate (up to 66%) inside heterogeneities, especially in air and bone heterogeneities, while the reduction of total photon dose rate was found less significant (up to 10%). In the presence of a heterogeneity, dose rate, fluence and energy spectrum were significantly different with respect to the homogenous phantom. The contribution of photon dose to the total dose in the presence of air and bone was dominant, compared to the neutron dose, whereas this photon contribution was reduced after passing the heterogeneity. As the bone heterogeneity size was increased from 1 × 1 × 1 cm3 to 1 × 3 × 1 cm3, the total dose and neutron energy fluence decreased of about 50% and 70%, respectively.

Towards Non-Invasive Diagnosis of Skin Cancer: Sensing Depth Investigation of Open-Ended Coaxial Probes.

Simple SummaryThis work investigates the effect of skin tissue heterogeneity on the sensing depth of the open-ended coaxial probe to exploit the potential use of the probe for skin cancer detection and to establish a simple measurement protocol for skin depth characterization. Skin depth was calculated through simulations and measurements. Heterogeneity was obtained using double-layered materials composed of gel-like skin mimicking material and liquid olive oil, triton X-100. It was concluded that the sensing depth was not dependent on the frequency between 0.5 to 6 GHz, was affected by the material located at the aperture of the probe, and lastly the dielectric property contrast between layers. Namely the degree of heterogeneity affects the probe sensing depth.Dielectric properties of biological tissues are traditionally measured with open-ended coaxial probes. Despite being commercially available for laboratory use, the technique suffers from high measurement error. This prevents the practical applications of the open-ended coaxial probes. One such application is the utilization of the technique for skin cancer detection. To enable a diagnostic tool, there is a need to address the error sources. Among others, tissue heterogeneity is a major contributor to measurement error. The effect of tissue heterogeneity on measurement accuracy can be decreased by quantifying the probe sensing depth. To this end, this work (1) investigates the sensing depth of the 2.2 mm-diameter open-ended coaxial probe for skin mimicking material and (2) offers a simple experimental setup and protocol for sensing depth characterization of open-ended coaxial probes. The sensing depth characterized through simulation and experiments using two double-layered configurations composed to mimic the skin tissue heterogeneity. Three thresholds in percent increase of dielectric property measurements were chosen to determine the sensing depth. Based on the experiment results, it was concluded that the sensing depth was effected by the dielectric property contrast between the layers. That is, high contrast results in rapid change whereas low contrast results in a slower change in measured dielectric properties. It was also concluded that the sensing depth was independent of frequency between 0.5 to 6 GHz and was mostly determined by the material located immediately at the aperture of the probe.

Regional and depth-dependence of cortical blood-flow assessed with high-resolution Arterial Spin Labeling (ASL)

Methods for imaging of cerebral blood flow do not typically resolve the cortex and thus underestimate flow. However, recent work with high-resolution MRI has emphasized the regional and depth-dependent structural, functional and relaxation times variations within the cortex. Using high-resolution Arterial Spin Labeling (ASL) and T1 mapping acquisitions, we sought to probe the effects of spatial resolution and tissue heterogeneity on cortical cerebral blood flow (CBF) measurements with ASL. We acquired high-resolution (1.6mm) 3 whole brain ASL data in a cohort of 10 volunteers at 3T, along with T1 and transit-time (ATT) mapping, followed by group cortical surface-based analysis using FreeSurfer of the different measured parameters. Fully resolved regional analysis showed higher than average mid-thickness CBF in primary motor areas (+15%,p<0.002), frontal regions (+17%,p<0.01) and auditory cortex, while occipital regions had lower average CBF (-20%,p<10−5). ASL signal was higher towards the pial surface but correction for the shorter T1 near the white matter surface reverses this gradient, at least when using the low-resolution ATT map. Similar to structural measures, fully-resolved ASL CBF measures show significant differences across cortical regions. Depth-dependent variation of T1 in the cortex complicates interpretation of depth-dependent ASL signal and may have implications for the accurate CBF quantification at lower resolutions.

Steering the Volume of Tissue Activated With a Directional Deep Brain Stimulation Lead in the Globus Pallidus Pars Interna: A Modeling Study With Heterogeneous Tissue Properties

Objective: To study the effect of directional deep brain stimulation (DBS) electrode configuration and vertical electrode spacing on the volume of tissue activated (VTA) in the globus pallidus, pars interna (GPi).Background: Directional DBS leads may allow clinicians to precisely direct current fields to different functional networks within traditionally targeted brain areas. Modeling the shape and size of the VTA for various monopolar or bipolar configurations can inform clinical programming strategies for GPi DBS. However, many computational models of VTA are limited by assuming tissue homogeneity.Methods: We generated a multimodal image-based detailed anatomical (MIDA) computational model with a directional DBS lead (1.5 mm or 0.5 mm vertical electrode spacing) placed with segmented contact 2 at the ventral posterolateral “sensorimotor” region of the GPi. The effect of tissue heterogeneity was examined by replacing the MIDA tissues with a homogeneous tissue of conductance 0.3 S/m. DBS pulses (amplitude: 1 mA, pulse width: 60 μs, frequency: 130 Hz) were used to produce VTAs. The following DBS contact configurations were tested: single-segment monopole (2B-/Case+), two-segment monopole (2A-/2B-/Case+ and 2B-/3B-/Case+), ring monopole (2A-/2B-/2C-/Case+), one-cathode three-anode bipole (2B-/3A+/3B+/3C+), three-cathode three-anode bipole (2A-/2B-/2C-/3A+/3B+/3C+). Additionally, certain vertical configurations were repeated with 2 mA current amplitude.Results: Using a heterogeneous tissue model affected both the size and shape of the VTA in GPi. Electrodes with both 0.5 mm and 1.5 mm vertical spacing (1 mA) modeling showed that the single segment monopolar VTA was entirely contained within the GPi when the active electrode is placed at the posterolateral “sensorimotor” GPi. Two segments in a same ring and ring settings, however, produced VTAs outside of the GPi border that spread into adjacent white matter pathways, e.g., optic tract and internal capsule. Both stacked monopolar settings and vertical bipolar settings allowed activation of structures dorsal to the GPi in addition to the GPi. Modeling of the stacked monopolar settings with the DBS lead with 0.5 mm vertical electrode spacing further restricted VTAs within the GPi, but the VTA volumes were smaller compared to the equivalent settings of 1.5 mm spacing.

An image-based geometric model for numerical simulation of blood perfusion within the liver lobules

An image-based numerical algorithm is presented for simulating blood flow through the liver tissue. First, a geometric model is constructed by applying image processing techniques on a real microscopic image of a liver tissue. Then, incompressible blood flow through liver lobules is simulated. Effects of tissue heterogeneity and deformity, presence/absence of the second central vein in a particular lobule, and apparent sinusoids density in the liver cross section on the blood flow are investigated. Numerical results indicate that the existence of thick low permeability vascular septum, high permeability sinusoids, and lobule tissue heterogeneity can considerably affect interlobular and intralobular blood flow.

Dosimetric characteristics of the INTRABEAM ® system with spherical applicators in the presence of air gaps and tissue heterogeneities.

The main aim of this study was to investigate the dosimetric characteristics of the INTRABEAM ® system in the presence of air gaps between the surface of applicators (APs) and tumor bed. Additionally, the effect of tissue heterogeneities was another focus. Investigating the dosimetric characteristics of the INTRABEAM® system is essential to deliver the required dose to the tumor bed correctly and reduce the delivered dose to the ribs and lung. Choosing the correct AP size and fitting it to the lumpectomy cavity is essential to remove the effect of air gaps and avoid inaccurate dose delivery. Consequently, the Geant4 toolkit was used to simulate the INTRABEAM ® system with spherical APs of various sizes. The wall effect of the ion chamber (IC) PTW 34013 used in the present study was checked. The simulations were validated in comparison with measurements, and then used to calculate any inaccuracies in dose delivery in the presence of 4- and 10-mm air gaps between the surface of the APs and the tumor bed. Also, the doses received due to tissue heterogeneities were characterized. It turned out that measurements and simulations were approximately in agreement (± 2%) for all sizes of APs. The perturbation factor introduced by the IC due to differences in graphite-coated polyethylene and air as compared to the phantom material was approximately equal to one for all AP. The greatest relative dose delivery difference was observed for an AP with a diameter of 1.5cm, i.e., 44% and 70% in the presence of 4- and 10-mm air gaps, respectively. In contrast, the lowest relative dose delivery difference was observed for an AP with a diameter of 5cm, i.e., 24% and 42% in the presence of 4- and 10-mm air gaps, respectively. Increasing APs size showed a decrease in relative dose delivery difference due to the presence of air gaps. In addition, the undesired dose received by the ribs turned out to be higher when a treatment site closer to the ribs was assumed. The undesired dose received by the ribs increased as the AP size increased. The lung dose turned out to be decreased due to the shielding effect of the ribs, small lung density, and long separation distance from the AP surface.

Modelling the action potential propagation in a heart with structural heterogeneities: From high-resolution MRI to numerical simulations.

Mathematical modelling and numerical simulation in cardiac electrophysiology have already been studied extensively. However, there is a clear lack of techniques and methodologies for studying the propagation of action potential in a heart with structural defects. In this article, we present a modified version of the bidomain model, derived using homogenisation techniques with the assumption of existence of diffusive inclusions in the cardiac tissue. The diffusive inclusions represent regions without electrically active myocytes, for example, fat, fibrosis, and so forth. We present an application of this model to a rat heart. Starting from high-resolution MRI, the geometry of the heart is built and meshed using image processing techniques. We perform a study of the effects of tissue heterogeneities induced by diffusive inclusions on the velocity and shape of the depolarisation wavefront. We present several test cases with different geometries of diffusive inclusions. We reach the conclusion that the conduction velocity is not affected in the best cases, while it is affected by up to 76% in the worst case scenario. Additionally, the shape of the wavefront was affected in some cases.

Quantitative Ultrasound Monitoring of Breast Tumour Response to Neoadjuvant Chemotherapy: Comparison of Results Among Clinical Scanners

Quantitative ultrasound (QUS) techniques have been demonstrated to detect cell death in vitro and in vivo. Recently, multi-feature classification models have been incorporated into QUS texture-feature analysis methods to increase further the sensitivity and specificity of detecting treatment response in locally advanced breast cancer patients. To effectively incorporate these analytic methods into clinical applications, QUS and texture-feature estimations should be independent of data acquisition systems. The study here investigated the consistencies of QUS and texture-feature estimation techniques relative to several factors. These included the ultrasound system properties, the effects of tissue heterogeneity and the effects of these factors on the monitoring of response to neoadjuvant chemotherapy. Specifically, tumour-response–detection performance based on QUS and texture parameters using two clinical ultrasound systems was compared. Observed variations in data between the systems were small and the results exhibited good agreement in tumour response predictions obtained from both ultrasound systems. The results obtained in this study suggest that tissue heterogeneity was a dominant feature in the parameters measured with the two different ultrasound systems; whereas differences in ultrasound system beam properties only exhibited a minor impact on texture features. The McNemar statistical test performed on tumour response prediction results from the two systems did not reveal significant differences. Overall, the results in this study demonstrate the potential to achieve reliable and consistent QUS and texture-based analyses across different ultrasound imaging platforms.

Implanted Nanosensors in Marine Organisms for Physiological Biologging: Design, Feasibility, and Species Variability.

In recent decades, biologists have sought to tag animals with various sensors to study aspects of their behavior otherwise inaccessible from controlled laboratory experiments. Despite this, chemical information, both environmental and physiological, remains challenging to collect despite its tremendous potential to elucidate a wide range of animal behaviors. In this work, we explore the design, feasibility, and data collection constraints of implantable, near-infrared fluorescent nanosensors based on DNA-wrapped single-wall carbon nanotubes (SWNT) embedded within a biocompatible poly(ethylene glycol) diacrylate (PEGDA) hydrogel. These sensors are enabled by Corona Phase Molecular Recognition (CoPhMoRe) to provide selective chemical detection for marine organism biologging. Riboflavin, a key nutrient in oxidative phosphorylation, is utilized as a model analyte in in vitro and ex vivo tissue measurements. Nine species of bony fish, sharks, eels, and turtles were utilized on site at Oceanogràfic in Valencia, Spain to investigate sensor design parameters, including implantation depth, sensor imaging and detection limits, fluence, and stability, as well as acute and long-term biocompatibility. Hydrogels were implanted subcutaneously and imaged using a customized, field-portable Raspberry Pi camera system. Hydrogels could be detected up to depths of 7 mm in the skin and muscle tissue of deceased teleost fish ( Sparus aurata and Stenotomus chrysops) and a deceased catshark ( Galeus melastomus). The effects of tissue heterogeneity on hydrogel delivery and fluorescence visibility were explored, with darker tissues masking hydrogel fluorescence. Hydrogels were implanted into a living eastern river cooter ( Pseudemys concinna), a European eel ( Anguilla anguilla), and a second species of catshark ( Scyliorhinus stellaris). The animals displayed no observable changes in movement and feeding patterns. Imaging by high-resolution ultrasound indicated no changes in tissue structure in the eel and catshark. In the turtle, some tissue reaction was detected upon dissection and histopathology. Analysis of movement patterns in sarasa comet goldfish ( Carassius auratus) indicated that the hydrogel implants did not affect swimming patterns. Taken together, these results indicate that this implantable form factor is a promising technique for biologging using aquatic vertebrates with further development. Future work will tune the sensor detection range to the physiological range of riboflavin, develop strategies to normalize sensor signal to account for the optical heterogeneity of animal tissues, and design a flexible, wearable device incorporating optoelectronic components that will enable sensor measurements in moving animals. This work advances the application of nanosensors to organisms beyond the commonly used rodent and zebrafish models and is an important step toward the physiological biologging of aquatic organisms.