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© 2015 IEEE. Terahertz (THz) spectral properties of human cornea are explored as a function of central corneal thickness (CCT) and corneal water content, and the clinical utility of THz-based corneal water content sensing is discussed. Three candidate corneal tissue water content (CTWC) perturbations, based on corneal physiology, are investigated that affect the axial water distribution and total thickness. The THz frequency reflectivity properties of the three CTWC perturbations were simulated and explored with varying system center frequency and bandwidths (Q-factors ). The modeling showed that at effective optical path lengths on the order of a wavelength the cornea presents a lossy etalon bordered by air at the anterior and the aqueous humor at the posterior. The simulated standing wave peak-to-valley ratio is pronounced at lower frequencies and its effect on acquired data can be modulated by adjusting the bandwidth of the sensing system. These observations are supported with experimental spectroscopic data. The results suggest that a priori knowledge of corneal thickness can be utilized for accurate assessments of corneal tissue water content. The physiologic variation of corneal thickness with respect to the wavelengths spanned by the THz band is extremely limited compared to all other structures in the body making CTWC sensing unique amongst all proposed applications of THz medical imaging.

Single-cell RNA sequencing has been widely used to investigate cell state transitions and gene dynamics of biological processes. Current strategies to infer the sequential dynamics of genes in a process typically rely on constructing cell pseudotime through cell trajectory inference. However, the presence of concurrent gene processes in the same group of cells and technical noise can obscure the true progression of the processes studied. To address this challenge, we present GeneTrajectory, an approach that identifies trajectories of genes rather than trajectories of cells. Specifically, optimal transport distances are calculated between gene distributions across the cell-cell graph to extract gene programs and define their gene pseudotemporal order. Here we demonstrate that GeneTrajectory accurately extracts progressive gene dynamics in myeloid lineage maturation. Moreover, we show that GeneTrajectory deconvolves key gene programs underlying mouse skin hair follicle dermal condensate differentiation that could not be resolved by cell trajectory approaches. GeneTrajectory facilitates the discovery of gene programs that control the changes and activities of biological processes., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Cutaneous lupus erythematosus (CLE) is a disfiguring autoimmune skin disease characterized by an inflammatory infiltrate rich in T cells, which are strongly implicated in tissue damage. How these cells adapt to the skin environment and promote tissue inflammation and damage is not known. In lupus nephritis, we previously identified an inflammatory gene program in kidney-infiltrating T cells that is dependent on HIF-1, a transcription factor critical for the cellular and developmental response to hypoxia as well as inflammation-associated signals. In our present studies using a mouse model of lupus skin disease, we find that skin-infiltrating CD4+ and CD8+ T cells also express high levels of HIF-1. Skin-infiltrating T cells demonstrated a strong cytotoxic signature at the transcript and protein levels, and HIF-1 inhibition abrogated skin and systemic diseases in association with decreased T cell cytotoxic activity. We also demonstrate in human CLE tissue that the T cell-rich inflammatory infiltrate exhibited increased amounts of HIF-1 and a cytotoxic signature. Granzyme B-expressing T cells were concentrated at sites of skin tissue damage in CLE, suggesting relevance of this pathway to human disease.

Objective: Medullary thyroid carcinoma (MTC) is a rare type of thyroid malignancy. Recently, a two-tier grading system (GS) for MTC has been suggested. We conducted this study to evaluate the generalizability, as well as application of recently proposed GS to our cohort of Medullary thyroid carcinoma (MTC) cases., Methods: We assigned grades to MTC cases and divided them into two groups by using morphologic criteria only as suggested by recent studies: low-grade (LG, <5 mitosis per 2 mm 2 , and no necrosis) and high-grade (HG, ≥5 mitosis per 2mm 2 or necrosis)., Results: A total of 59 MTC cases were evaluated and of those 52 (88 %) were LG and 7 (12 %) were HG. Vascular invasion (VI) (p = 0.017), distant metastasis (DM) (p < 0.0001), nuclear pleomorphism (NP) (p = 0.017) and prominent nucleoli (p = 0.03) were prominently noted in the HG group. After controlling for demographics using multivariate cox regression, tumor grade and necrosis remained significantly associated with the overall survival (HR = 22.7, p < 0.01 and HR = 11.1, p = 0.008, respectively). Upon comparing the cases with and without nodal disease, we found that nodal disease is more strongly associated with NP (p = 0.029), tumor fibrosis (p = 0.0001), VI (p = 0.001) and DM (p = 0.005)., Conclusions: We applied the two-tier GS for MTC to our cohort of cases and found statistically significant differences in the overall survival among the two groups. Adding the grading to the pathology report communicates additional information regarding risk stratification in MTC., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this paper, we develop an efficient algorithm to evaluate the azimuthal Fourier components of the Green's function for the Helmholtz equation in cylindrical coordinates. A computationally efficient algorithm for this modal Green's function is essential for solvers for electromagnetic scattering from bodies of revolution (e.g., radar cross sections, antennas). Current algorithms to evaluate this modal Green's function become computationally intractable when the source and target are close or when the wavenumber is large or complex. Furthermore, most state-of-the-art methods cannot be easily parallelized. In this paper, we present an algorithm for evaluating the modal Green's function that has performance independent of both source-to-target proximity and wavenumber, and whose cost grows as O ( m ), where m is the Fourier mode. Our algorithm's performance is independent of whether the wavenumber is real or complex. Furthermore, our algorithm is embarrassingly parallelizable.

Competing Interests: None.

Background: Activating point mutations of the RAS gene (NRAS, HRAS, and KRAS) can be seen in benign and malignant thyroid tumors; among these, NRAS mutations are more commonly seen. This study was conducted to evaluate the thyroid risk of malignancy (ROM) associated with RAS mutations in thyroid fine-needle aspiration (FNA) at the authors' institution., Methods: The authors searched their electronic database system between January 2015 and May 2021 for thyroid FNA cases with any type of RAS mutation. Molecular alterations were identified with the ThyroSeq Genomic Classifier, ThyGeNEXT (thyroid oncogene panel)/ThyraMIR (miRNA classifier), or ThyroSure gene panel., Results: A total of 127 cases (age, 51 ± 14 years; 100 females and 27 males) were identified, and 72 had histologic follow-up. The overall ROM associated with RAS mutations (with or without any other molecular alterations) was 29%, whereas the ROM was lower (18%) with RAS mutations only. Isolated NRAS, HRAS, and KRAS mutation-associated ROMs were 15%, 27%, and 14%, respectively. Among these RAS-mutated cases, the cases with a Bethesda category IV cytologic diagnosis had a higher ROM than the cases with a category III diagnosis (38% vs 17%). Twenty-one histologically confirmed malignant cases were mostly classified on cytology as category IV lesions (14 of 34; 41%), and the remainder were either category III (6 of 35; 17%) or V lesions (1 of 1; 100%)., Conclusions: This study demonstrated that the overall RAS mutation-associated ROM in thyroid FNA was intermediate (29%), and isolated HRAS mutations appeared to have a higher ROM (27%) than NRAS and KRAS mutations (15% and 14%, respectively)., (© 2021 American Cancer Society.)

Objectives: Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy, and early diagnosis, often aided by fine-needle aspiration (FNA), is key to improving patient prognosis. While the current literature describes some of the cytologic features (CFs) of this entity, a comprehensive examination of the CFs has not yet been performed., Methods: We retrospectively searched our electronic database for ATC cases with available slides between January 2008 and December 2019. Cases were examined for 22 CFs and compared with a control group of differentiated thyroid carcinoma., Results: A total of 18 ATC cases meeting our inclusion criteria were identified. Most cases showed moderate to high cellularity (83%) and epithelioid cytomorphology (83%). Architecture included either predominantly groups/clusters of tumor cells (56%) or single tumor cells (44%). The other CFs were as follows: nuclear enlargement (100%), nuclear crowding (89%), nuclear membrane irregularities (100%), multinucleated tumor cells (33%), and background acute inflammatory cells (50%). Of the CFs examined, statistically significant differences between ATC and the control groups were found in the following: nuclear pleomorphism, coarse/clumped chromatin, macronucleoli, apoptosis, and necrosis., Conclusions: Identification of key CFs in FNA coupled with the clinical history aids in the diagnosis of ATC and helps distinguish it from other mimickers., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Single-cell RNA-sequencing data has revolutionized our ability to understand of the patterns of cell-cell and ligand-receptor connectivity that influence the function of tissues and organs. However, the quantification and visualization of these patterns in a way that informs tissue biology are major computational and epistemological challenges. Here, we present Connectome, a software package for R which facilitates rapid calculation and interactive exploration of cell-cell signaling network topologies contained in single-cell RNA-sequencing data. Connectome can be used with any reference set of known ligand-receptor mechanisms. It has built-in functionality to facilitate differential and comparative connectomics, in which signaling networks are compared between tissue systems. Connectome focuses on computational and graphical tools designed to analyze and explore cell-cell connectivity patterns across disparate single-cell datasets and reveal biologic insight. We present approaches to quantify focused network topologies and discuss some of the biologic theory leading to their design., (© 2022. The Author(s).)

Context.—: Large cell transformation (LCT) of indolent B-cell lymphomas, such as follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL), signals a worse prognosis, at which point aggressive chemotherapy is initiated. Although LCT is relatively straightforward to diagnose in lymph nodes, a marrow biopsy is often obtained first given its ease of procedure, low cost, and low morbidity. However, consensus criteria for LCT in bone marrow have not been established., Objective.—: To study the accuracy and reproducibility of a trained convolutional neural network in identifying LCT, in light of promising machine learning tools that may introduce greater objectivity to morphologic analysis., Design.—: We retrospectively identified patients who had a diagnosis of FL or CLL who had undergone bone marrow biopsy for the clinical question of LCT. We scored morphologic criteria and correlated results with clinical disease progression. In addition, whole slide scans were annotated into patches to train convolutional neural networks to discriminate between small and large tumor cells and to predict the patient's probability of transformation., Results.—: Using morphologic examination, the proportion of large lymphoma cells (≥10% in FL and ≥30% in CLL), chromatin pattern, distinct nucleoli, and proliferation index were significantly correlated with LCT in FL and CLL. Compared to pathologist-derived estimates, machine-generated quantification demonstrated better reproducibility and stronger correlation with final outcome data., Conclusions.—: These histologic findings may serve as indications of LCT in bone marrow biopsies. The pathologist-augmented with machine system appeared to be the most predictive, arguing for greater efforts to validate and implement these tools to further enhance physician practice.

Background: There is a critical need to improve support for families making difficult shared decisions about patient care with clinicians in the neuroscience ICU (neuro-ICU). The aim of this study is to identify patient- and family-related factors associated with dissatisfaction with shared decision-making support among families of neuro-critically ill patients., Methods: We conducted a retrospective observational cohort study using survey data that had been collected from a consecutive sample of family members of patients in the neuro-ICU (one family member per patient) at two US academic centers. Satisfaction with shared decision-making support on ICU discharge had been measured among family members using one specific Likert scale item on the Family Satisfaction in the ICU 24 survey, a validated survey instrument for families of patients in the ICU. We dichotomized top-box responses for this particular item as an outcome variable and identified available patient- and family-related covariates associated with dissatisfaction (i.e., less than complete satisfaction) via univariate and multivariate analyses., Results: Among 355 surveys, 180 (49.5%) of the surveys indicated dissatisfaction with support during decision-making. In a multivariate model, no preexisting characteristics of families or patients ascertainable on ICU admission were predictive of dissatisfaction. However, among family factors determined during the ICU course, experiencing three or fewer formal family meetings (odds ratio 1.93 [confidence interval 1.13-3.31]; p = 0.01) was significantly predictive of dissatisfaction with decisional support in this cohort with an average patient length of stay of 8.6 days (SD 8.4). There was also a trend toward a family's decision to keep a patient as full code, without treatment limitations, being predictive of dissatisfaction (odds ratio 1.80 [confidence interval 0.93-3.51]; p = 0.08)., Conclusions: Family dissatisfaction with neuro-ICU shared decision-making support is not necessarily predicted by any preexisting family or patient variables but appears to correlate with participating in fewer formal family meetings during ICU admission. Future studies to improve family satisfaction with neurocritical care decision-making support should have broad inclusion criteria for participants and should consider promoting frequency of family meetings as a core strategy., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: This study investigated p16 by immunohistochemistry (IHC) on cellblocks (CBs) and human papillomavirus (HPV) by polymerase chain reaction (PCR) in fine-needle aspiration (FNA) of head and neck squamous cell carcinoma (HNSCC)., Methods: Receiver operating characteristic (ROC) curve analysis was used to assess test performance in CBs compared with p16 IHC in 42 surgical specimens from patients with HNSCC and in correlation with HPV by PCR in cytology specimens. The study assessed HPV by PCR in FNA specimens as a substitute for p16 IHC in surgical specimens., Results: Of 42 cases, 38 CBs showed malignant cells as cohesive clusters of viable cells with or without single tumor cells, whereas 4 specimens were composed exclusively of single tumor cells and degenerated cells. All p16-negative surgical specimens showed an absence of p16 staining in the corresponding CBs (n = 16). In the p16-positive surgical cases (n = 26), corresponding CBs with tumor clusters (n = 23) showed heterogeneous p16 expression ranging from 40% to 100%; however, scoring single cells was challenging and unreliable because of cellular degradation. ROC curve inspection showed the optimal threshold to be at least 40% p16 staining in tumor clusters with 100% sensitivity and specificity. In cases with inadequate CBs, HPV by PCR on needle rinse showed 88% sensitivity and 100% specificity for p16 expression in surgical specimens., Conclusions: A cutoff of at least 40% p16 expression in tumor clusters may be appropriate for p16 positivity in cytology CB specimens. A positive HPV finding by PCR on needle rinse can be used as a substitute for p16 expression in surgical specimens., (© 2020 American Cancer Society.)

A method to register THz and visible images of cutaneous burn wounds and to calibrate THz image data is presented. Images of partial and full thickness burn wounds in 9 rats were collected over 435 mins. = 7.25 hours following burn induction. A two-step process was developed to reference the unknown structure of THz imaging contrast to the known structure and the features present in visible images of the injury. This process enabled the demarcation of a wound center for each THz image, independent of THz contrast. Threshold based segmentation enabled the automated identification of air (0% reflectivity), brass (100% reflectivity), and abdomen regions within the registered THz images. Pixel populations, defined by the segmentations, informed unsupervised image calibration and contrast warping for display. The registered images revealed that the largest variation in THz tissue reflectivity occurred superior to the contact region at ~0.13%/min. Conversely the contact region showed demonstrated an ~6.5-fold decrease at ~0.02%/min. Exploration of occlusion effects suggests that window contact may affect the measured edematous response., Competing Interests: The authors declare that there are no conflicts of interest related to this article.

Terahertz (THz) imaging of corneal tissue water content (CTWC) is a proposed method for early, accurate detection and study of corneal diseases. Despite promising results from ex vivo and in vivo cornea studies, interpretation of the reflectivity data is confounded by the contact between corneal tissue and rigid dielectric window used to flatten the imaging field. This work develops a novel imaging system and image reconstruction methods specifically for nearly spherical targets such as human cornea. A prototype system was constructed using a 650 GHz multiplier source and Schottky diode detector. Resolution and imaging field strength measurement from characterization targets correlate well with those predicted by the quasioptical theory and physical optics analysis. Imaging experiments with corneal phantoms and ex vivo corneas demonstrate the hydration sensitivity of the imaging system and reliable measurement of CTWC. We present successful acquisition of non-contact THz images of in vivo human cornea, and discuss strategies for optimizing the imaging system design for clinical use.

Reflection mode Terahertz (THz) imaging of corneal tissue water content (CTWC) is a proposed method for early, accurate detection and study of corneal diseases. Despite promising results from ex vivo and in vivo cornea studies, interpretation of the reflectivity data is confounded by the contact between corneal tissue and dielectric windows used to flatten the imaging field. Herein, we present an optical design for non-contact THz imaging of cornea. A beam scanning methodology performs angular, normal incidence sweeps of a focused beam over the corneal surface while keeping the source, detector, and patient stationary. A quasioptical analysis method is developed to analyze the theoretical resolution and imaging field intensity profile. These results are compared to the electric field distribution computed with a physical optics analysis code. Imaging experiments validate the optical theories behind the design and suggest that quasioptical methods are sufficient for designing of THz corneal imaging systems. Successful imaging operations support the feasibility of non-contact in vivo imaging. We believe that this optical system design will enable the first, clinically relevant, in vivo exploration of CTWC using THz technology.

Background: Head and neck squamous cell carcinomas (HNSCCs) are debilitating diseases for which a patient's prognosis depends heavily on complete tumor resection. Currently, the surgeon's fingers determine the location of tissue margins. This study evaluated the diagnostic utility of a novel imaging modality, dynamic optical contrast imaging (DOCI), in the detection of HNSCC. This system generates contrast by illuminating the tissue with pulsed light and detecting variations in endogenous fluorophore lifetimes., Methods: A total of 47 fresh ex vivo samples from 15 patients were imaged with the DOCI system immediately after surgical resection. DOCI maps were analyzed to determine the statistical significance of contrast between tumors and adjacent nonmalignant tissue. Pilot intraoperative clinical data were also acquired., Results: Statistical significance (P < .05) between muscle and tumor was established for 10 of 10 emission wavelengths, between collagen and tumor for 8 of 10 emission wavelengths, and between fat and tumor for 2 of 10 wavelengths. The system extracted relative fluorescence decay information in a surgically relevant field of view in <2 minutes., Conclusions: This study demonstrates the feasibility of using DOCI to rapidly and accurately distinguish HNSCC from surrounding normal tissue. An analysis of DOCI images revealed microscopic characterization sufficient for tissue-type identification consistent with histology. Such an intraoperative tool would be transformative by allowing the rapid delineation of tumor tissue from nontumor tissue and thus maximizing the efficacy of resection and improving patient outcomes. Cancer 2017;123:879-86. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

The variable location and indistinct features of parathyroid glands can make their intraoperative identification challenging. Currently, there exists no routine use of localization methods during surgery. Dynamic optical contrast imaging (DOCI) leverages a novel realization of temporally dependent measurements of tissue autofluorescence that allows the acquisition of specific tissue properties. A prospective series of patients with primary hyperparathyroidism was examined. Parathyroid lesions and surrounding tissues were collected; fluorescence decay images were acquired via DOCI. Ex vivo samples (81 patients) were processed for histologic assessment. DOCI extracts relative fluorescence decay information in a surgically relevant field of view with a clinically accessible acquisition time <2 minutes. Analysis of DOCI revealed microscopic characterization sufficient for tissue type identification consistent with histology ( P < .05). DOCI is capable of efficiently distinguishing parathyroid tissue from adjacent tissues. Such an intraoperative tool would be transformative, helping surgeons to identify lesions, preserve healthy tissue, and improve patient outcomes.

Purpose: Focal laser ablation is an investigational technique to treat prostate cancer in a region confined manner via coagulative necrosis. This phase I trial primarily examines the safety of transrectal magnetic resonance imaging guided (in-bore) focal laser ablation in men with intermediate risk prostate cancer. An exploratory end point is cancer control after 6 months., Materials and Methods: In an institutional review board approved trial we studied focal laser ablation in 8 men with intermediate risk prostate cancer diagnosed using magnetic resonance-ultrasound fusion. Focal laser ablation was performed by inserting a cylindrically diffusing, water cooled laser fiber into magnetic resonance visible regions of interest, followed by interstitial heating at 10 to 15 W for up to 3 minutes. Secondary safety monitors (thermal probes) were inserted to assess the accuracy of magnetic resonance thermometry. Comprehensive magnetic resonance-ultrasound fusion biopsy was performed after 6 months. Adverse events and health related quality of life questionnaires were recorded., Results: Focal laser ablation was successfully performed in all 8 subjects. No grade 3 or greater adverse events occurred and no changes in International Prostate Symptom Score or International Index of Erectile Function 5 were observed. Ablation zones, as measured by posttreatment magnetic resonance imaging, had a median volume of 3 cc or 7.7% of prostate volume. Prostate specific antigen decreased in 7 men (p <0.01). At followup magnetic resonance-ultrasound fusion biopsy cancer was not detected in the ablation zone in 5 men but was present outside the treatment margin in 6 men., Conclusions: Focal laser ablation of the prostate is feasible and safe in men with intermediate risk prostate cancer without serious adverse events or changes in urinary or sexual function at 6 months. Comprehensive biopsy followup indicates that larger treatment margins than previously thought necessary may be required for complete tumor ablation., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

A pulsed terahertz (THz) imaging system and millimeter-wave reflectometer were used to acquire images and point measurements, respectively, of five rabbit cornea in vivo . These imaging results are the first ever produced of in vivo cornea. A modified version of a standard protocol using a gentle stream of air and a Mylar window was employed to slightly dehydrate healthy cornea. The sensor data and companion central corneal thickness (CCT) measurements were acquired every 10-15 min over the course of two hours using ultrasound pachymmetry.. Statistically significant positive correlations were established between CCT measurements and millimeter wave reflectivity. Local shifts in reflectivity contrast were observed in the THz imagery; however, the THz reflectivity did not display a significant correlation with thickness in the region probed by the 100 GHz and CCT measurements. This is explained in part by a thickness sensitivity at least 10× higher in the mm-wave than the THz systems. Stratified media and effective media modeling suggest that the protocol perturbed the thickness and not the corneal tissue water content (CTWC). To further explore possible etalon effects, an additional rabbit was euthanized and millimeter wave measurements were obtained during death induced edema. These observations represent the first time that the uncoupled sensing of CTWC and CCT have been achieved in vivo .

This paper presents a novel THz optical design that allows the acquisition of THz reflectivity maps of in vivo cornea without the need for a field flattening window and preliminary imaging results of in vivo rabbit cornea. The system's intended use is to sense small changes in corneal tissue water content (CTWC) that can be precursors for a host of diseases and pathologies. Unique beam optics allows the scanning of a curved surface at normal incidence while keeping the source detector and target stationary. Basic system design principles are discussed and image sets of spherical calibration targets and corneal phantom models are presented. The presented design will enable, for the first time, non-contact THz imaging of animal and human cornea.

We have developed a system for evaluating magnetic resonance imaging of prostate cancer, using patient-specific 3D printed molds to facilitate MR-histology correlation. Prior to radical prostatectomy a patient receives a multiparametric MRI, which an expert genitourinary radiologist uses to identify and contour regions suspicious for disease. The same MR series is used to generate a prostate contour, which is the basis for design of a patient-specific mold. The 3D printed mold contains a series of evenly spaced parallel slits, each of which corresponds to a known MRI slice. After surgery, the patient's specimen is enclosed within the mold, and all whole-mount levels are obtained simultaneously through use of a multi-bladed slicing device. The levels are then formalin fixed, processed, and delivered to an expert pathologist, who identifies and grades all lesions within the slides. Finally, the lesion contours are loaded into custom software, which elastically warps them to fit the MR prostate contour. The suspicious regions on MR can then be directly compared to lesions on histology. Furthermore, the false-negative and false-positive regions on MR can be retrospectively examined, with the ultimate goal of developing methods for improving the predictive accuracy of MRI. This work presents the details of our analysis method, following a patient from diagnosis through the MR-histology correlation process. For this patient MRI successfully predicted the presence of cancer, but true lesion volume and extent were underestimated. Most cancer-positive regions missed on MR were observed to have patterns of low T2 signal, suggesting that there is potential to improve sensitivity.

In the absence of an imaging technique that provides imagery of diseased tissue with high diagnostic accuracy and contrast, surgeons must often excise excess healthy tissue surrounding neoplasms to ensure complete removal of malignant tissues. Additional approaches that are commonly used in the detection of tumor regions include palpation and conventional ultrasound to locate the affected area. However, these techniques suffer from limitations such as minimal specificity and lack of depth penetration. Lack of specificity results in the production of unclear diseased tissue regions, and therefore fails to offer surgeons a reliable and accurate image guidance tool. The proposed work provides an alternative diagnostic modality termed ultrasound-stimulated vibro-acoustography (USVA) that aims to generate detailed images characterized by viscoelastic properties of tissues. We demonstrate selective imaging using phantom tissue samples of polyvinyl alcohol (PVA) that are altered and arranged into unique geometries of varying elastic topology. Determining the precision and sensitivity of the USVA imaging system in identifying boundary regions as well as intensity ranges associated with tissue phantom targets will provide additional important information to allow for a non-invasive tool to distinguish diseased tissues from normal tissues in an in vivo setting.