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The analysis for collagen density for the AsPC-1 (left) and BxPC-3 (right) tumor in relation to tumor shear modulus. (a) and (b) sonograms of representative AsPC-1 tumor and a BxPC-3 tumors. The corresponding shear modulus elastograms (c) and (d). The Masson's Trichrome stained histological images are shown in (e) to (f). (g) scatter plot of mean collagen density as a function of mean shear modulus.

Purpose:High tissue pressure prevents chemotherapeutics from reaching the core of pancreatic tumors. Therefore, targeted therapies have been developed to reduce this pressure. While point probes have shown the effectiveness of these pressure-reducing therapies via single-location estimates, ultrasound elastography is now widely available as an imaging technique to provide real-time spatial maps of shear modulus (tissue stiffness). However, the relationship between shear modulus and the underlying tumor microenvironmental causes of high tissue pressure has not been investigated. In this work, elastography was used to investigate how shear modulus influences drug delivery in situ, and how it correlates with collagen density, hyaluronic acid content, and patent vessel density—features of the tumor microenvironment known to influence tissue pressure.Experimental Design:Intravenous injection of verteporfin, an approved human fluorescent drug, was used in two pancreatic cancer xenograft models [AsPC-1 (n = 25) and BxPC-3 (n = 25)].Results:Fluorescence intensity was higher in AsPC-1 tumors than in BxPC-3 tumors (P < 0.0001). Comparing drug uptake images and shear wave elastographic images with histologic images revealed that: (i) drug delivery and shear modulus were inversely related, (ii) shear modulus increased linearly with increasing collagen density, and (iii) shear modulus was marginally correlated with the local assessment of hyaluronic acid content.Conclusions:These results demonstrate that elastography could guide targeted therapy and/or identify patients with highly elevated tissue pressure.See related commentary by Nia et al., p. 2024

Aiming at the problems that most of the existing electromagnetic metasurfaces have single function and narrow application scope, a highly integrated lightning-type metasurface is proposed in this study. It can realize the functions of circular dichroism (CD), absorption of electromagnetic waves, broadband x-to-y cross polarization conversion (CPC) function, linear-to-circular polarization conversion (LTC-PC) function and asymmetric transmission (AT), and its functions are also analyzed and verified. The designed metasurface consists of the bottom grating structure, the lower SiO2, the middle lightning-type graphene, the upper SiO2, the top graphene and photosensitive silicon. Through numerical calculations, the CD of design can reach more than 85% at 4.22 THz. The function of bimodal absorption is achieved at 4.09 and 8.69 THz. At 7.41∼8.21 THz, the polarization conversion ratio (PCR) of the metasurface reaches more than 99%. Simultaneously, the function of LTC-PC can be formed when PCR is 50%. Finally, when the designed metasurface is in the transmissive state, the AT of design is close to 60% at 7.84 THz. This design provides a new design idea and method for biomedical detection, image processing, modulators, smart switches, optical diodes and other fields.

We report a demonstration of an ultrafast all-optical switching with unique light control effects. The all-optical switching consists of a gold film with asymmetric split rings and a silica substrate. The device effectively controls the transmission and absorption of continuous pulses in the communication band (1200-1800 nm) and short pulses with a pulse duration of 80 fs by using the interaction of two coherent beams on nano-metamaterials with a thickness of only 50 nm. The metamaterial can achieve more than 90 % output control under continuous light irradiation. When the pulse duration is 80 fs, the switching contrast ratio is greater than 3 : 1 and the modulation bandwidth is greater than 12.5 THz. Switching time can be on the order of femtosecond. This paper provides a new structure for ultra-high speed optical data processing components in coherent networks.

Objective: Tumor stiffening in pancreatic adenocarcinoma (PDAC) has been linked to cancer progression and lack of therapy response, yet current elastography tools cannot map stiffness in a whole tumor field-of-view with biologically relevant spatial resolution. Therefore, this study was developed to assess stiffness heterogeneity and geometrical patterns across whole PDAC xenograft ex vivo tumors. Methods: The ex vivo elastography (EVE) mapping system was capable of creating stiffness map at 300-micron spatial resolution under a 5–20 mm field of view relevant to whole tumor assessment. The stiffness value at each location was determined by compression testing and an absolute tumor Young's modulus map was calculated based on the calibration between the system and ultrasound elastography (R2 = 0.95). Results: Two PDAC tumor lines AsPC-1 and BxPC-3 implanted in xenograft models were assessed to show tumor stiffness and its linear relationship to collagen content (R2 = 0.59). EVE was able to capture stiffness heterogeneity ranging between 5 and 100 kPa in pancreatic tumors with collagen content up to 25%. More importantly, data shows the inverse relationship of local stiffness to local drug distribution (R2 = 0.66) and vessel patency (R2 = 0.61) in both PDAC tumor lines. Conclusion: The results suggested that elastography could be utilized to predict drug penetration in PDAC tumors or assess response to biological modifying adjunct therapies. Significance: This study presents the first attempt to map out stiffness on a biologically relevant spatial scale across whole PDAC tumor slices with spatial resolution in the hundreds of microns.

Background: Tomato gray leaf spot caused by Stemphylium lycopersici (S. lycopersici) is a serious disease that can severely hinder tomato production. To date, only Sm has been reported to provide resistance against this disease, and the molecular mechanism underlying resistance to this disease in tomato remains unclear. To better understand the mechanism of tomato resistance to S. lycopersici, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR)-based analysis, physiological indexes, microscopy observations and transgenic technology were used in this study.Results: Our results showed that the expression of SlERF01 was strongly induced by S. lycopersici and by exogenous applications of the hormones salicylic acid (SA) and jasmonic acid (JA). Furthermore, overexpression of SlERF01 enhanced the hypersensitive response (HR) to S. lycopersici and elevated the expression of defense genes in tomato. Furthermore, the accumulation of lignin, callose and hydrogen peroxide (H2O2) increased in the transgenic lines after inoculation with S. lycopersici. Taken together, our results showed that SlERF01 played an indispensable role in multiple SA, JA and reactive oxygen species (ROS) signaling pathways to provide resistance to S. lycopersici invasion. Our findings also indicated that SlERF01 could activate the expression of the PR1 gene and enhance resistance to S. lycopersici.Conclusions: We identified the SlERF01 gene, which encodes a novel tomato AP2/ERF transcription factor (TF). Functional analysis revealed that SlERF01 positively regulates tomato resistance to S. lycopersici. Our findings indicate that SlERF01 plays a key role in multiple SA, JA and ROS signaling pathways to provide resistance to invasion by S. lycopersici. The findings of this study not only help to better understand the mechanisms of response to pathogens but also enable targeted breeding strategies for tomato resistance to S. lycopersici.

Gray leaf spot (GLS), caused by Stemphylium lycopersici (S. lycopersici), is one of the most devastating diseases in tomato (Solanum lycopersicum). The resistance (R) gene, Sm, conferring high resistance to S. lycopersici, was introgressed into cultivated tomatoes from the wild tomato species Solanum pimpinellifolium (S. pimpinellifolium). Recently, several studies reported the mapping of the Sm gene. To date, however, it has not been cloned yet. Here, we cloned this resistance gene using a map-based cloning strategy. The Sm gene was mapped in a 160 kb interval of Chromosome 11 between two markers, M390 and M410, by using an F2 population from a cross between the resistant cultivar ‘Motelle’ (Mt) and susceptible line ‘Moneymaker’ (Mm). Three clustered NBS-LRR resistance genes, Solyc11g020080 (R1), Solyc11g020090 (R2) and Solyc11g020100 (R3) were identified in this interval. Nonsynonymous SNPs were identified only in the ORF of R3, supporting it may be a strong candidate gene for Sm. Furthermore, gene silencing of R3 abolished the high resistance to S. lycopersici in Motelle, demonstrating that it is the gene that confers high resistance to S. lycopersici. The clone of Sm gene will provide new opportunities for innovative breeding strategies to breed multi-resistant tomato cultivars.

Gray leaf spot (GLS) resistance in tomato is controlled by one major dominant locus, Sm. Sm was fine mapped, and the nucleotide-binding site-leucine-rich repeat (NBS-LRR) gene Solyc11g020100 was identified as a candidate gene for Sm. Further functional analysis indicated that this gene confers high resistance to Stemphylium lycopersici in tomato. Tomato (Solanum Lycopersicum) is widely consumed and cultivated in the world. Gray leaf spot (GLS), caused by Stemphylium lycopersici (S. lycopersici), is one of the most devastating diseases in tomato production. To date, only one resistance gene, Sm, which confers high resistance against GLS disease, has been identified in the wild tomato species Solanum pimpinellifolium. This resistance locus (comprising the Sm gene) has been transferred into the cultivated variety 'Motelle'. Although several studies have reported the mapping of the Sm gene, it has not been cloned, limiting the utilization in tomato breeding. Here, we cloned Sm using a map-based cloning strategy. The Sm gene was mapped in a region of 160 kb at chromosome 11 between two markers, namely, M390 and M410, by using an F

Background Leaves, which are the most important organs of plants, can not only fix carbon sources through photosynthesis, but also absorb nutrients through transpiration. Leaf development directly determines the growth, flowering and fruiting of plants. There are many factors that affect leaf development, such as the growth environment, gene expression, and hormone synthesis. In this study, tomatoes were used to study the role of the transcription factor Solanum lycopersicum salt-related MYB1-like (SlSRM1-like) in the development of tomato leaves. Results Loss-of-function of the SlSRM1-like gene mediated by clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated 9 (Cas9) resulted in abnormal tomato leaf morphology, including thinner leaves, wrinkled edges, raised veins, disordered edge veins, and left and right asymmetry. An analysis of the transcription levels of genes related to leaf development revealed that the expression of these genes was significantly altered in the SlSRM1-like mutants (SlSRM1-like-Ms). Moreover, the SlSRM1-like gene was expressed at higher transcription levels in young tissues than in old tissues, and its expression was also induced in response to auxin. In addition, the transcription levels of genes related to the auxin pathway, which regulates tomato growth and development, were severely affected in the SlSRM1-like-Ms. Therefore, it is hypothesized that the SlSRM1-like gene functions in the regulation of tomato leaf development through the auxin-related pathway. Conclusions In this study, we successfully knocked out the SlSRM1-like gene in the tomato variety Ailsa Craig using CRISPR technology and found that knockout of the SlSRM1-like gene resulted in abnormal development of tomato leaves. Further research indicated that SlSRM1-like regulated tomato leaf development through auxin-related pathways. The results provide an important reference for the functional study of other SRM1-like genes in plants and provide new insights into the regulation of leaf development in tomato and other plants.

Flowering is a morphogenetic process in which angiosperms shift from vegetative growth to reproductive growth. Flowering time has a strong influence on fruit growth, which is closely related to productivity. Therefore, research on crop flowering time is particularly important. To better understand the flowering period of the tomato, we performed transcriptome sequencing of early flower buds and flowers during the extension period in the later-flowering “Moneymaker” material and the earlier-flowering “20965” homozygous inbred line, and we analyzed the obtained data. At least 43.92 million clean reads were obtained from 12 datasets, and the similarity with the tomato internal reference genome was 92.86–94.57%. Based on gene expression and background annotations, 49 candidate genes related to flowering time and flower development were initially screened, among which the greatest number belong to the photoperiod pathway. According to the expression pattern of candidate genes, the cause of early flowering of “20965” is predicted. The modes of action of the differentially expressed genes were classified, and the results show that they are closely related to hormone regulation and participated in a variety of life activities in crops. The candidate genes we screened and the analysis of their expression patterns provide a basis for future functional verification, helping to explore the molecular mechanism of tomato flowering time more comprehensively.

Background APETALA2/ethylene responsive factor (AP2/ERF) transcription factors are a plant-specific family of transcription factors and one of the largest families of transcription factors. Ethylene response factors (ERF) regulate plant growth, development, and responses to biotic and abiotic stress. In a previous study, the ERF2 gene was significantly upregulated in both resistant and susceptible tomato cultivars in response to Stemphylium lycopersici. The main purpose of this study was to systematically analyze the ERF family and to explore the mechanism of ERF2 in tomato plants resisting pathogen infection by the Virus-induced Gene Silencing technique. Results In this experiment, 134 ERF genes were explored and subjected to bioinformatic analysis and divided into twelve groups. The spatiotemporal expression characteristics of ERF transcription factor gene family in tomato were diverse. Combined with RNA-seq, we found that the expression of 18 ERF transcription factors increased after inoculation with S. lycopersici. In ERF2-silenced plants, the susceptible phenotype was observed after inoculation with S. lycopersici. The hypersensitive response and ROS production were decreased in the ERF2-silenced plants. Physiological analyses showed that the superoxide dismutase, peroxidase and catalase activities were lower in ERF2-silenced plants than in control plants, and the SA and JA contents were lower in ERF2-silenced plants than in control plants after inoculation with S. lycopersici. Furthermore, the results indicated that ERF2 may directly or indirectly regulate Pto, PR1b1 and PR-P2 expression and enhance tomato resistance. Conclusions In this study, we identified and analyzed members of the tomato ERF family by bioinformatics methods and classified, described and analyzed these genes. Subsequently, we used VIGS technology to significantly reduce the expression of ERF2 in tomatoes. The results showed that ERF2 had a positive effect on tomato resistance to S. lycopersici. Interestingly, ERF2 played a key role in multiple SA, JA and ROS signaling pathways to confer resistance to invasion by S. lycopersici. In addition, ERF2 may directly or indirectly regulate Pto, PR1b1 and PR-P2 expression and enhance tomato resistance to S. lycopersici. In summary, this study provides gene resources for breeding for disease resistance in tomato.

Background: APETALA2/ethylene responsive factor (AP2/ERF) transcription factors are a plant-specific family of transcription factors and one of the largest families of transcription factors. Ethylene response factors (ERF) regulate plant growth, development, and responses to biotic and abiotic stress. In a previous study, the ERF2 gene was significantly upregulated in both resistant and susceptible tomato cultivars in response to Stemphylium lycopersici. The main purpose of this study was to systematically analyze the ERF family and to explore the mechanism of ERF2 in tomato plants resisting pathogen infection by the Virus-induced Gene Silencing technique.Results: In this experiment, 134 ERF genes were explored and subjected to bioinformatic analysis and divided into twelve groups. The spatiotemporal expression characteristics of ERF transcription factor gene family in tomato were diverse. Combined with RNA-seq, we found that the expression of 18 ERF transcription factors increased after inoculation with S. lycopersici. In ERF2-silenced plants, the susceptible phenotype was observed after inoculation with S. lycopersici. The hypersensitive response and ROS production were decreased in the ERF2-silenced plants. Physiological analyses showed that the superoxide dismutase, peroxidase and catalase activities were lower in ERF2-silenced plants than in control plants, and the SA and JA contents were lower in ERF2-silenced plants than in control plants after inoculation with S. lycopersici. Furthermore, the results indicated that ERF2 may directly or indirectly regulate Pto, PR1b1 and PR-P2 expression and enhance tomato resistance.Conclusions: In this study, we identified and analyzed members of the tomato ERF family by bioinformatics methods and classified, described and analyzed these genes. Subsequently, we used VIGS technology to significantly reduce the expression of ERF2 in tomatoes. The results showed that ERF2 had a positive effect on tomato resistance to S. lycopersici. Interestingly, ERF2 played a key role in multiple SA, JA and ROS signaling pathways to confer resistance to invasion by S. lycopersici. In addition, ERF2 may directly or indirectly regulate Pto, PR1b1 and PR-P2 expression and enhance tomato resistance to S. lycopersici. In summary, this study provides gene resources for breeding for disease resistance in tomato.

Background: APETALA2/ethylene responsive factor (AP2/ERF) transcription factors are a plant-specific family of transcription factors and one of the largest families of transcription factors. Ethylene response factors (ERF) regulate plant growth, development, and responses to biotic and abiotic stress. In a previous study, the ERF2 gene was significantly upregulated in both resistant and susceptible tomato cultivars in response to Stemphylium lycopersici. The main purpose of this study was to systematically analyze the ERF family and to explore the mechanism of ERF2 in tomato plants resisting pathogen infection by the Virus-induced Gene Silencing (VIGS) technique.Results: In this experiment, 134 ERF genes were explored and subjected to bioinformatic analysis. This experiment divided 134 ERF members into twelve groups based on the conserved domain of the genes. The spatiotemporal expression characteristics of ERF transcription factor family genes in tomato were diverse. Combined with RNA-seq, we found that the expression of 18 ERF transcription factors increased after inoculation with S. lycopersici. In ERF2-silenced plants, the susceptible phenotype was observed after inoculation with S. lycopersici. The hypersensitive response and ROS production were decreased in the ERF2-silenced plants. Physiological analyses showed that the superoxide dismutase, peroxidase and catalase activities were lower in ERF2-silenced plants than in control plants, and the SA and JA contents were lower in ERF2-silenced plants than in control plants after inoculation with S. lycopersici. Furthermore, the results indicated that ERF2 may directly or indirectly regulate Pto, PR1b1 and PR-P2 expression and enhance tomato resistance.Conclusions: In this study, we identified and analyzed members of the tomato ERF family by bioinformatics methods and classified, described and analyzed these genes. Subsequently, we used VIGS technology to significantly reduce the expression of ERF2 in tomatoes. The results showed that ERF2 had a positive effect on tomato resistance to S. lycopersici. Interestingly, ERF2 played a key role in multiple SA, JA and ROS signaling pathways to confer resistance to invasion by S. lycopersici. In addition, ERF2 may directly or indirectly regulate Pto, PR1b1 and PR-P2 expression and enhance tomato resistance to S. lycopersici. In summary, this study provides gene resources for breeding for disease resistance in tomato.

Many factors affecting satellitism tests are unclear, and it is difficult to avoid misidentification, even if the medium is properly selected. We investigated the factors causing false-positive results for Haemophilus influenzae and false-negative results for Haemophilus parainfluenzae in the satellitism tests using Staphylococcus aureus as the source of nicotinamide adenine dinucleotide (NAD). H. influenzae (four reference strains and 47 clinical isolates), H. parainfluenzae (two reference strains and 67 clinical isolates), four different media, and two strains of S. aureus revived on two different media were used in this study. The type of medium used to revive S. aureus was the most common factor causing false-positive results for H. influenzae, followed by different strains of S. aureus and the type of medium used for the experiment. The production of false-negative results for H. parainfluenzae was only related to the medium used in the experiment. To improve the accuracy of the tests in routine laboratories, using S. aureus as the source of NAD, tryptic soy agar, and S. aureus (ATCC 25923) revived on nutrient agar should be adopted.

Background: Tomato gray leaf spot caused by Stemphylium lycopersici (S. lycopersici) is a serious disease that can severely hinder tomato production. To date, only Sm has been reported to provide resistance against this disease, and the molecular mechanism underlying resistance to this disease in tomato remains unclear. To better understand the mechanism of tomato resistance to S. lycopersici, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR)-based analysis, physiological indexes, microscopy observations and transgenic technology were used in this study.Results: Our results showed that the expression of SlERF01 was strongly induced by S. lycopersici and by exogenous applications of the hormones salicylic acid (SA) and jasmonic acid (JA). Furthermore, overexpression of SlERF01 enhanced the hypersensitive response (HR) to S. lycopersici and elevated the expression of defense genes in tomato. Furthermore, the accumulation of lignin, callose and hydrogen peroxide (H2O2) increased in the transgenic lines after inoculation with S. lycopersici. Taken together, our results showed that SlERF01 played an indispensable role in multiple SA, JA and reactive oxygen species (ROS) signaling pathways to provide resistance to S. lycopersici invasion. Our findings also indicated that SlERF01 could activate the expression of the PR1 gene and enhance resistance to S. lycopersici.Conclusions: We identified the SlERF01 gene, which encodes a novel tomato AP2/ERF transcription factor (TF). Functional analysis revealed that SlERF01 positively regulates tomato resistance to S. lycopersici. Our findings indicate that SlERF01 plays a key role in multiple SA, JA and ROS signaling pathways to provide resistance to invasion by S. lycopersici. The findings of this study not only help to better understand the mechanisms of response to pathogens but also enable targeted breeding strategies for tomato resistance to S. lycopersici.

Background: Many factors affecting satellitism test are not clear, and it is difficult to avoid misidentified even if the medium is properly selected. We investigated the factors that cause false positives of Haemophilus influenzae and false negatives of Haemophilus parainfluenzae in the satellitism test supplemented V factor by Staphylococcus aureus.Methods: H. influenzae (four reference strains and 47 clinical isolates), H. parainfluenzae (two reference strains and 67 clinical isolates), four different media, and two strains of S. aureus activated on two different media were involved in this study.Results: The type of medium used to activate S. aureus was the most common factor causing false positives of H. influenzae, followed by the strain of S. aureus, and again the type of medium used for the experiment. The production of false negatives of H. parainfluenzae was only related to the medium used in the experiment.Conclusions: Tryptic soy agar and S. aureus (ATCC 25923) activated with nutrient agar should be used in the satellitism test for Haemophilus spp. to improve the accuracy of the test.

Additional file 1: Table S1. Primers used in this study.

Tunable multi-function metasurfaces have become the latest research frontiers in planar optics. In this study, a dynamically tunable plasmon-induced transparency (PIT) structure based on a graphene split-ring resonator and graphene ribbon is proposed. The influences of the structural parameters and graphene Fermi energy on the PIT response were investigated both analytically and numerically simulations. The inclusion of an additional vanadium dioxide (VO2) substrate layer enables the metasurface to achieve dynamic switching between PIT and perfect absorption using the phase change property of VO2. The new metasurface device exhibits the PIT effect when the VO2 layer is in an insulating state and acts as a perfect absorber when it is in a metallic state. Moreover, the response of the two functions can be easily adjusted dynamically by changing the Fermi energy of graphene. In addition, both functions were highly sensitive to changes in the ambient refractive index. The results of this work have potential applications in slow-light devices, optical switches, modulators, perfect absorbers, highly sensitive sensors, and multifunctional devices.

This study describes some results concerning the hybrid process of ultraviolet/chlorine (UV/chlorine) as a pre-oxidation strategy prior to ultrafiltration for the treatment of natural organic matter (NOM)-contaminated surface water. Chlorine has been extensively used in water treatment since it can act as disinfectant or coagulant aid. In addition, the combination of UV and chlorine, compared to the other oxidants generally used in water treatment, offers a potentially effective and cheaper alternative for pre-oxidation process. Parallel tests with or without the application of chlorine were conducted to evaluate the effect of chlorine dosage on the increase of trans-membrane pressure under low dosage of UV irradiation. The results showed that UV/chlorine pre-oxidation achieved remarkable reduction of both total membrane fouling (49%) and reversible membrane fouling (59%) at 4 mg/L dose of chlorine as a result of the removal of both high molecular weight (MW) (1–20 kDa) humic substances and lower MW compounds. Hybrid process of UV/chlorine and UF membrane achieved significant removal of DOC (34%) and UV254 (49%) at chlorine dosage of 4 mg/L and a UV dosage of 180 mJ/cm2. Modeling fit results indicated that the NOM-related membrane fouling mitigation was probably attributed to the alleviation of intermediate pore blocking and standard pore blocking with intermediate pore blocking playing a more important role. Additionally, the UV/chlorine unit could have a bright prospect for engineering application as it performed better in cost control as pretreatment prior to UF membrane compared to other pre-oxidation processes.

High tissue pressures prevent chemotherapeutics from reaching the parenchyma of pancreatic ductal adenocarcinoma, which makes it difficult to treat this aggressive disease. Researchers currently use invasive probes to monitor the effectiveness of pressure-reducing therapies, but this practice introduces additional complications. Here, we hypothesize that Young’s modulus is a good surrogate for tissue pressure because collagen density and hyaluoronic acid, the key features of the tumor microenvironment responsible for high tissue pressures, also affect modulus elastograms. To corroborate this hypothesis, we used model-based quasi-static elastography to assess how the Young’s modulus of naturally occurring AsPc-1 pancreatic tumors varies with collagen density and hyaluoronic acid concentration. We observed that Young’s moduli of orthotopically grown xenograft tumors were 6 kPa (p < 0.05) higher than that of their subcutaneously grown counterparts. We also observed a strong correlation between Young’s modulus and regions within the tumors with high collagen (R2 ≈ 0.8) and hyaluoronic acid (R2 ≈ 0.6) densities. These preliminary results indicate that hyaluronic acid and collagen density, features of the pancreatic ductal adenocarcinoma tumor microenvironment responsible for high tissue pressure, influence Young’s modulus.

Increased arterial thickness measured with ultrasound correlates with future cardiovascular events, but conventional ultrasound imaging techniques cannot distinguish between intima, media, or atherosclerotic plaque in the carotid artery. In this work, we evaluated how well vascular elastography can detect intimal changes in a mouse model of carotid remodeling. We ligated the left external and internal branches of the carotid artery of male FVB mice and performed sham operations for 2 weeks. High-resolution ultrasound imaging accurately detected lower blood velocities and low blood volume flow in the carotid arteries after ligation in FVB mice. However, ultrasound could not detect differences in the carotid wall even at 2 weeks post-surgery. The Young’s modulus was measured based on displacements of the carotid artery wall, and Young’s modulus was 2-fold greater in shams at 1 week post ligation, and 3-fold greater 2 weeks after ligation. Finally, the higher Young’s modulus was most associated with higher intimal thickness but not medial or adventitial thickness as measured by histology. In conclusion, we developed a robust ultrasound-based elastography method for early detection of intimal changes in small animals.

Neither contrast-enhanced computed tomography nor magnetic resonance imaging can monitor changes in pancreatic ductal adenocarcinoma (PDAC) microenvironment during therapy. We hypothesized that shear wave elastography (SWE) could overcome this limitation. To test this hypothesis, we measured the shear modulus of two groups of murine pancreatic tumors (KCKO, n = 30; PAN02, n = 30) treated with stereotactic body radiation therapy (SBRT). The mean shear modulus of KCKO tumors was 7.651 kPa higher than those of PAN02 tumors (p < 0.001). SBRT reduced the shear modulus in KCKO tumors by 8.914 kPa (p < 0.001). No significant difference in the shear modulus of SBRT-treated PAN02 tumors was observed. Additionally, necrotic and collagen densities were reduced only in the SBRT-treated KCKO tumors. Shear modulus was dependent on collagen distribution and histological texture parameters (i.e., entropy and fractional dimension). Shear wave elastography imaging differentiate between SBRT responsive tumors (KCKO) and unresponsive ones (PAN02).

Pancreatic cancer is an aggressive disease a 5-year-survival rate less than 7%. To improve the patient overall survival, recent developments in pancreatic cancer research have been targeting various components of the tumor microenvironment such as the extracellular matrix, blood vessels and immune cells. We hypothesize that targeted therapies will affect the biomechanics of the tumor microenvironment. To corroborate this hypothesis, we used shear wave elasticity imaging (SWEI) to investigate how different therapies (immunotherapy and radiotherapy) impact tumor stiffness.

Pancreatic ductal adenocarcinoma (PDA) is a common and lethal disease, with a 5-year survival rate of less than 6%. The absence of a functional vasculature and the build-up of dense stromal regions impede drug delivery that prevents the disease from being eradicated, even when surgery is combined with chemotherapy. We hypothesize that real-time measurement of total tissue pressure, as related to cancer cell growth and drug delivery, will enable translational research into patient-specific therapies. Since no imaging methods can measure tissue pressure in vivo, we investigated the feasibility of using elastography to provide a surrogate measure of total tissue pressure. Specifically, we performed studies on orthotopically and subcutaneously grown xenograft tumors (n = 20) to assess how the shear modulus of naturally occurring AsPc-1 pancreatic tumors varies with stromal density. The results of this investigation revealed that there is 6 kPa difference between the shear modulus of orthotopically and subcuta...