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Article: Characterizing breast cancer response to neoadjuvant therapy based on biophysical modeling and multiparametric magnetic resonance imaging data.

Bowers, Haley J / Guthrie, John A / Krukoski, Alaura / Thomas, Alexandra / Weis, Jared A

medRxiv : the preprint server for health sciences

2023

Abstract: Personalized medicine efforts are focused on identifying biomarkers to guide individualizing neoadjuvant therapy regimens. In this work, we aim to validate a previously developed image data-driven mathematical modeling approach for dynamic ... ...

Abstract	Personalized medicine efforts are focused on identifying biomarkers to guide individualizing neoadjuvant therapy regimens. In this work, we aim to validate a previously developed image data-driven mathematical modeling approach for dynamic characterization of breast cancer response to neoadjuvant therapy using a large, multi-site cohort. We retrospectively analyzed patients enrolled in the BMMR2 ACRIN 6698 subset at 10 institutions. Patients enrolled received four MRI examinations during neoadjuvant therapy with acquisitions at baseline (T
Language	English
Publishing date	2023-11-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.28.23299112
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Developing a biomechanical model-based elasticity imaging method for assessing hormone receptor positive breast cancer treatment-related myocardial stiffness changes.

Miller, Caroline E / Jordan, Jennifer H / Thomas, Alexandra / Weis, Jared A

Journal of medical imaging (Bellingham, Wash.)

2021 Volume 8, Issue 5, Page(s) 56002

Abstract: Purpose: ...

Abstract	Purpose:
Language	English
Publishing date	2021-09-30
Publishing country	United States
Document type	Journal Article
ISSN	2329-4302
ISSN	2329-4302
DOI	10.1117/1.JMI.8.5.056002
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Reproducibility assessment of a biomechanical model-based elasticity imaging method for identifying changes in left ventricular mechanical stiffness.

Miller, Caroline E / Jordan, Jennifer H / Douglas, Emily / Ansley, Katherine / Thomas, Alexandra / Weis, Jared A

Journal of medical imaging (Bellingham, Wash.)

2022 Volume 9, Issue 5, Page(s) 56001

Abstract: Purpose: Cardiotoxicity of antineoplastic therapies is increasingly a risk to cancer patients treated with curative intent with years of life to protect. Studies highlight the importance of identifying early cardiac decline in cancer patients undergoing ...

Abstract	Purpose: Cardiotoxicity of antineoplastic therapies is increasingly a risk to cancer patients treated with curative intent with years of life to protect. Studies highlight the importance of identifying early cardiac decline in cancer patients undergoing cardiotoxic therapies. Accurate tools to study this are a critical clinical need. Current and emerging methods for assessing cardiotoxicity are too coarse for identifying preclinical cardiac degradation or too cumbersome for clinical implementation. Approach: In the previous work, we developed a noninvasive biomechanical model-based elasticity imaging methodology (BEIM) to assess mechanical stiffness changes of the left ventricle (LV) based on routine cine cardiac magnetic resonance (CMR) images. We examine this methodology to assess methodological reproducibility. We assessed a cohort of 10 participants that underwent test/retest short-axis CMR imaging at baseline and follow-up sessions as part of a previous publicly available study. We compare test images to retest images acquired within the same session to assess within-session reproducibility. We also compare test and retest images acquired at the baseline imaging session to test and retest images acquired at the follow-up imaging session to assess between-session reproducibility. Results: We establish the within-session and between-session reproducibility of our method, with global elasticity demonstrating repeatability within a range previously demonstrated in cardiac strain imaging studies. We demonstrate increased repeatability of global elasticity compared to segmental elasticity for both within-session and between-session. Within-subject coefficients of variation for within-session test/retest images globally for all modulus directions and a mechanical fractional mechanical stiffness anisotropy metric ranged from 11% to 28%. Conclusions: Results suggest that our methodology can reproducibly generate estimates of relative mechanical elasticity of the LV and provides a threshold for distinguishing true changes in myocardial mechanical stiffness from experimental variation. BEIM has applications in identifying preclinical cardiotoxicity in breast cancer patients undergoing antineoplastic therapies.
Language	English
Publishing date	2022-10-22
Publishing country	United States
Document type	Journal Article
ISSN	2329-4302
ISSN	2329-4302
DOI	10.1117/1.JMI.9.5.056001
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Article ; Online: Dynamic characterization of breast cancer response to neoadjuvant therapy using biophysical metrics of spatial proliferation.

Bowers, Haley J / Douglas, Emily / Ansley, Katherine / Thomas, Alexandra / Weis, Jared A

Scientific reports

2022 Volume 12, Issue 1, Page(s) 11718

Abstract: Current tools to assess breast cancer response to neoadjuvant chemotherapy cannot reliably predict disease eradication, which if possible, could allow early cessation of therapy. In this work, we assessed the ability of an image data-driven mathematical ... ...

Abstract	Current tools to assess breast cancer response to neoadjuvant chemotherapy cannot reliably predict disease eradication, which if possible, could allow early cessation of therapy. In this work, we assessed the ability of an image data-driven mathematical modeling approach for dynamic characterization of breast cancer response to neoadjuvant therapy. We retrospectively analyzed patients enrolled in the I-SPY 2 TRIAL at the Atrium Health Wake Forest Baptist Comprehensive Cancer Center. Patients enrolled on the study received four MR imaging examinations during neoadjuvant therapy with acquisitions at baseline (T
MeSH term(s)	Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Cell Proliferation ; Female ; Humans ; Neoadjuvant Therapy/methods ; Retrospective Studies ; Treatment Outcome
Language	English
Publishing date	2022-07-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-15801-7
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Article: Myocardial Elasticity Imaging Correlates with Histopathology in a Model of Anthracycline-Induced Cardiotoxicity.

Miller, Caroline E / Jordan, Jennifer H / Thomas, Alexandra / Friday, Sarah R / Meléndez, Giselle C / Weis, Jared A

bioRxiv : the preprint server for biology

2023

Abstract: Background: There is considerable focus on developing strategies for identifying subclinical cardiac decline prior to cardiac failure. Myocardial tissue elasticity changes may precede irreversible cardiac damage, providing promise for an early biomarker ...

Abstract	Background: There is considerable focus on developing strategies for identifying subclinical cardiac decline prior to cardiac failure. Myocardial tissue elasticity changes may precede irreversible cardiac damage, providing promise for an early biomarker for cardiac decline. Biomarker strategies are of particular interest in cardio-oncology due to cardiotoxic effects of anti-neoplastic therapies, particularly anthracycline-based chemotherapeutics. Current clinical methods for diagnosing cardiotoxicity are too coarse to identify cardiac decline early enough for meaningful therapeutic intervention, or too cumbersome for clinical implementation. Methods: Utilizing changes in myocardial elasticity as a biomarker for subclinical cardiac decline, we developed a biomechanical model-based elasticity imaging methodology (BEIM) to estimate spatial maps of left ventricle (LV) myocardial elasticity. In this study, we employ this methodology to assess changes in LV elasticity in a non-human primate model of doxorubicin-induced cardiotoxicity. Cardiac magnetic resonance imaging of five African Green monkeys was acquired at baseline prior to doxorubicin administration, 6-weeks, and 15-weeks after final doxorubicin dose and histopathological samples of the LV were taken at 15-weeks after final doxorubicin dose. Spatial elasticity maps of the mid-short axis plane of the LV were estimated at each image acquisition. Global and regional LV elasticity were calculated and changes between imaging time points was assessed. LV elasticity at baseline and final time point were compared to cardiomyocyte size and collagen volume fraction measurements calculated from histopathological staining of archived tissue bank samples and study endpoint tissue samples utilizing Pearson's correlation coefficients. Results: We identify significant changes in LV elasticity between each imaging time point both globally and regionally. We also demonstrate strong correlation between LV elasticity and cardiomyocyte size and collagen volume fraction measurements. Results indicate that LV elasticity estimates calculated using BEIM correlate with histopathological changes that occur due to doxorubicin administration, validating LV elasticity solutions and providing significant promise for use of BEIM to non-invasively elucidate cardiac injury. Conclusions: This methodology can show progressive changes in LV elasticity and has potential to be a more sensitive indicator of elasticity changes than current clinical measures of cardiotoxicity. LV elasticity may provide a valuable biomarker for cardiotoxic effects of anthracycline-based chemotherapeutics and cardiac disease detection.
Language	English
Publishing date	2023-10-16
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.11.561881
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Article ; Online: Characterization of multicellular breast tumor spheroids using image data-driven biophysical mathematical modeling.

Bowers, Haley J / Fannin, Emily E / Thomas, Alexandra / Weis, Jared A

Scientific reports

2020 Volume 10, Issue 1, Page(s) 11583

Abstract: Multicellular tumor spheroid (MCTS) systems provide an in vitro cell culture model system which mimics many of the complexities of an in vivo solid tumor and tumor microenvironment, and are often used to study cancer cell growth and drug efficacy. Here, ... ...

Abstract	Multicellular tumor spheroid (MCTS) systems provide an in vitro cell culture model system which mimics many of the complexities of an in vivo solid tumor and tumor microenvironment, and are often used to study cancer cell growth and drug efficacy. Here, we present a coupled experimental-computational framework to estimate phenotypic growth and biophysical tumor microenvironment properties. This novel framework utilizes standard microscopy imaging of MCTS systems to drive a biophysical mathematical model of MCTS growth and mechanical interactions. By extending our previous in vivo mechanically-coupled reaction-diffusion modeling framework we developed a microscopy image processing framework capable of mechanistic characterization of MCTS systems. Using MDA-MB-231 breast cancer MCTS, we estimated biophysical parameters of cellular diffusion, rate of cellular proliferation, and cellular tractions forces. We found significant differences in these model-based biophysical parameters throughout the treatment time course between untreated and treated MCTS systems, whereas traditional size-based morphometric parameters were inconclusive. The proposed experimental-computational framework estimates mechanistic MCTS growth and invasion parameters with significant potential to assist in better and more precise assessment of in vitro drug efficacy through the development of computational analysis methodologies for three-dimensional cell culture systems to improve the development and evaluation of antineoplastic drugs.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Biophysical Phenomena ; Breast Neoplasms/chemistry ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/drug therapy ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Drug Screening Assays, Antitumor ; Female ; Humans ; Mammary Neoplasms, Animal/chemistry ; Mammary Neoplasms, Animal/drug therapy ; Mammary Neoplasms, Animal/pathology ; Models, Theoretical ; Spheroids, Cellular/chemistry ; Spheroids, Cellular/drug effects ; Spheroids, Cellular/ultrastructure ; Tumor Microenvironment/drug effects
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2020-07-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-68324-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Chief cell plasticity is the origin of metaplasia following acute injury in the stomach mucosa.

Caldwell, Brianna / Meyer, Anne R / Weis, Jared A / Engevik, Amy C / Choi, Eunyoung

Gut

2021 Volume 71, Issue 6, Page(s) 1068–1077

Abstract: Objective: Metaplasia arises from differentiated cell types in response to injury and is considered a precursor in many cancers. Heterogeneous cell lineages are present in the reparative metaplastic mucosa with response to injury, including foveolar ... ...

Abstract	Objective: Metaplasia arises from differentiated cell types in response to injury and is considered a precursor in many cancers. Heterogeneous cell lineages are present in the reparative metaplastic mucosa with response to injury, including foveolar cells, proliferating cells and spasmolytic polypeptide-expressing metaplasia (SPEM) cells, a key metaplastic cell population. Zymogen-secreting chief cells are long-lived cells in the stomach mucosa and have been considered the origin of SPEM cells; however, a conflicting paradigm has proposed isthmal progenitor cells as an origin for SPEM. Design: Gastric intrinsic factor (GIF) is a stomach tissue-specific gene and exhibits protein expression unique to mature mouse chief cells. We generated a novel chief cell-specific driver mouse allele, GIF-rtTA. GIF-GFP reporter mice were used to validate specificity of GIF-rtTA driver in chief cells. GIF-Cre-RnTnG mice were used to perform lineage tracing during homoeostasis and acute metaplasia development. L635 treatment was used to induce acute mucosal injury and coimmunofluorescence staining was performed for various gastric lineage markers. Results: We demonstrated that mature chief cells, rather than isthmal progenitor cells, serve as the predominant origin of SPEM cells during the metaplastic process after acute mucosal injury. Furthermore, we observed long-term label-retaining chief cells at 1 year after the GFP labelling in chief cells. However, only a very small subset of the long-term label-retaining chief cells displayed the reprogramming ability in homoeostasis. In contrast, we identified chief cell-originating SPEM cells as contributing to lineages within foveolar cell hyperplasia in response to the acute mucosal injury. Conclusion: Our study provides pivotal evidence for cell plasticity and lineage contributions from differentiated gastric chief cells during acute metaplasia development.
MeSH term(s)	Animals ; Cell Plasticity ; Chief Cells, Gastric/metabolism ; Gastric Mucosa/metabolism ; Humans ; Metaplasia/metabolism ; Mice ; Stomach ; Stomach Neoplasms/metabolism
Language	English
Publishing date	2021-09-08
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gutjnl-2021-325310
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Article: Photoacoustic Imaging for Non-Invasive Assessment of Physiological Biomarkers of Intestinal Injury in Experimental Necrotizing Enterocolitis.

Weis, Jared A / Rauh, Jessica L / Ellison, Maryssa A / Cruz-Diaz, Nildris / Yamaleyeva, Liliya M / Welch, Cherrie D / Zeller, Kristen A / Weis, Victoria G

bioRxiv : the preprint server for biology

2023

Abstract: Background: Necrotizing enterocolitis (NEC) is an often-lethal disease of the premature infants' intestinal tract that is exacerbated by significant difficulties in early and accurate diagnosis. In NEC disease, the intestine often exhibits hypoperfusion ...

Abstract	Background: Necrotizing enterocolitis (NEC) is an often-lethal disease of the premature infants' intestinal tract that is exacerbated by significant difficulties in early and accurate diagnosis. In NEC disease, the intestine often exhibits hypoperfusion and dysmotility, which contributes to advanced disease pathogenesis. However, these physiological features cannot be accurately and quantitively assessed within the current constraints of imaging modalities frequently used in the clinic (plain film X-ray and ultrasound). We have previously demonstrated the ability of photoacoustic imaging (PAI) to non-invasively and quantitively assess intestinal tissue oxygenation and motility in a healthy neonatal rat model. As a first-in-disease application, we evaluated NEC pathogenesis using PAI to assess intestinal health biomarkers in a preclinical neonatal rat experimental model of NEC. Methods: NEC was induced in neonatal rat pups from birth to 4 days old via hypertonic formula feeding, full-body hypoxic stress, and lipopolysaccharide administration to mimic bacterial colonization. Healthy breastfed (BF) controls and NEC rat pups were imaged at 2- and 4-days old. Intestinal tissue oxygen saturation was measured with PAI imaging for oxy- and deoxyhemoglobin levels. To measure intestinal motility, ultrasound and co-registered PAI cine recordings were used to capture intestinal peristalsis motion and contrast agent (indocyanine green) transit within the intestinal lumen. Additionally, both midplane two-dimensional and volumetric three-dimensional imaging acquisitions were assessed for oxygenation and motility. Results: NEC pups showed a significant decrease of intestinal tissue oxygenation as compared to healthy BF controls at both ages (2-days old: 55.90% +/- 3.77% vs 44.12% +/- 7.18%; 4-days old: 56.13% +/- 3.52% vs 38.86% +/- 8.33%). Intestinal motility, assessed using a computational intestinal deformation analysis, demonstrated a significant reduction in the intestinal motility index in both early (2-day) and established (4-day) NEC. Extensive NEC damage was confirmed with histology and dysmotility was confirmed by small intestinal transit assay. Conclusions: This study presents PAI as a successful emerging diagnostic imaging modality for both intestinal tissue oxygenation and intestinal motility disease hallmarks in a rat NEC model. PAI presents enormous significance and potential for fundamentally changing current clinical paradigms for detecting and monitoring intestinal pathologies in the premature infant.
Language	English
Publishing date	2023-10-23
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.20.563296
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Article: Accounting for intraoperative brain shift ascribable to cavity collapse during intracranial tumor resection.

Narasimhan, Saramati / Weis, Jared A / Luo, Ma / Simpson, Amber L / Thompson, Reid C / Miga, Michael I

Journal of medical imaging (Bellingham, Wash.)

2020 Volume 7, Issue 3, Page(s) 31506

Abstract: Purpose: ...

Abstract	Purpose:
Language	English
Publishing date	2020-06-22
Publishing country	United States
Document type	Journal Article
ISSN	2329-4302
ISSN	2329-4302
DOI	10.1117/1.JMI.7.3.031506
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Article: Photoacoustic Imaging as a Novel Non-Invasive Biomarker to Assess Intestinal Tissue Oxygenation and Motility in Neonatal Rats.

Weis, Victoria G / Cruz-Diaz, Nildris / Rauh, Jessica L / Ellison, Maryssa A / Yamaleyeva, Liliya M / Welch, Cherrie D / Zeller, Kristen A / Weis, Jared A

bioRxiv : the preprint server for biology

2023

Language	English
Publishing date	2023-06-27
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.06.27.545971
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