Browsing by Author "Gosling, Sarah"

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    Breast cancer at the micrometre scale
    (Cranfield University, 2020-11-27 09:28) Gosling, Sarah
    Microcalcifications are deposits of calcium phosphate commonly found in association with some types of breast cancer. Calcifications are usually detected as bright white spots on a mammogram. Diagnosis of some breast diseases is linked to the morphology and distribution of microcalcifications, but these deposits are rarely investigated as individual entities.Multiple techniques have been used to investigate individual calcifications, including histological staining (H&E), scanning electron microscopy (SEM), elemental analysis (EDS) and x-ray diffraction (XRD). Together, these techniques allow a better understanding of the structure of the crystalline and tissue elements of breast calcifications at the micrometre scale, which may provide an insight in their formation mechanisms and possible functions. Ultimately, deciphering calcification chemistry could lead to their use as novel prognostic markers for breast disease.
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    Breast microcalcifications as biomarkers of tissue pathology
    (Cranfield University, 2020-01-09 11:31) Gosling, Sarah
    Breast cancer is the most commonly diagnosed cancer in women in the UK, accounting for 31% of all cases. Some breast malignancies, known as in-situ cancers, have the potential to form invasive cancer, but this is not true in all cases. There is significant overtreatment of in-situ cancers, which can be a traumatic process for patients. Therefore, a robust method to determine which of these malignancies will develop into clinically significant invasive cancer is required. Ductal carcinoma in-situ (DCIS), the most common in-situ breast cancer, has associated calcium deposits (microcalcifications) in 80-90% of cases. Microcalcifications are therefore an important diagnostic indicator of DCIS. These microcalcifications are composed of hydroxyapatite, a nano-crystalline calcium phosphate, with the potential for high levels of ion substitution.The crystalline nature of hydroxyapatite permits the use of X-ray diffraction to investigate the microstructure of microcalcifications found in breast tissue. X-ray diffraction patterns can be used to determine properties such as crystallite size, irregularities in the crystal lattice and give indications about the ions present. Together, differences in these parameters may permit the development of a novel prognostic marker for different breast tissue pathologies.
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    Calcification microstructure reflects breast tissue microenvironment
    (Springer, 2019-12-05) Gosling, Sarah; Scott, Robert; Greenwood, Charlene; Bouzy, Pascaline; Nallala, Jayakrupakar; Lyburn, Iain Douglas; Stone, Nicholas; Rogers, Keith
    Microcalcifications are important diagnostic indicators of disease in breast tissue. Tissue microenvironments differ in many aspects between normal and cancerous cells, notably extracellular pH and glycolytic respiration. Hydroxyapatite microcalcification microstructure is also found to differ between tissue pathologies, including differential ion substitutions and the presence of additional crystallographic phases. Distinguishing between tissue pathologies at an early stage is essential to improve patient experience and diagnostic accuracy, leading to better disease outcome. This study explores the hypothesis that microenvironment features may become immortalised within calcification crystallite characteristics thus becoming indicators of tissue pathology. In total, 55 breast calcifications incorporating 3 tissue pathologies (benign – B2, ductal carcinoma in-situ - B5a and invasive malignancy - B5b) from archive formalin-fixed paraffin-embedded core needle breast biopsies were analysed using X-ray diffraction. Crystallite size and strain were determined from 548 diffractograms using Williamson-Hall analysis. There was an increased crystallinity of hydroxyapatite with tissue malignancy compared to benign tissue. Coherence length was significantly correlated with pathology grade in all basis crystallographic directions (P < 0.01), with a greater difference between benign and in situ disease compared to in-situ disease and invasive malignancy. Crystallite size and non-uniform strain contributed to peak broadening in all three pathologies. Furthermore, crystallite size and non-uniform strain normal to the basal planes increased significantly with malignancy (P < 0.05). Our findings support the view that tissue microenvironments can influence differing formation mechanisms of hydroxyapatite through acidic precursors, leading to differential substitution of carbonate into the hydroxide and phosphate sites, causing significant changes in crystallite size and non-uniform strain.
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    Data for: Anisotropy visualisation from X-ray diffraction of biological apatite in mixed phase samples
    (Cranfield University, 2024-09-06) Scott, Robert; Rogers, Keith; Gosling, Sarah; Arnold, Emily
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    High Resolution Mapping of DCIS Breast Microcalcifications
    (Cranfield University, 2019-11-19 15:38) Gosling, Sarah
    Breast cancer accounts for 31% of all cancers in women in the UK, making it the most common female cancer. Ductal carcinoma in-situ (DCIS), a malignancy confined to the ducts of the breast, is an increasingly diagnosed cancer which is highly associated with calcium deposits (microcalcifications). Microcalcifications are associated with both benign and malignant conditions and are predominantly composed of hydroxyapatite (calcium phosphate), which has a highly substitutable structure. Therefore, microcalcifications may be important diagnostic indicators of breast malignancy.X-ray diffraction was used, for the first time, to investigate the crystallographic properties of hydroxyapatite in microcalcifications. High-resolution mapping of individual calcifications from a single sample of ductal carcinoma in-situ was carried out to investigate variability of crystallographic parameters within single calcifications, and between calcifications of the same sample. Crystallite size and non-uniform strain are two key crystallographic properties investigated in this study. Numerous parameters showed significant variability both within individual calcifications and between calcifications from the same sample. For most calcifications, values of crystallite size were significantly greater towards the centre of calcifications, however this was not true of all calcifications. This high-resolution approach has revealed potential differential formation mechanisms of calcifications in breast tissue extracted from the same patient. Calcifications may provide an exciting insight into the mechanisms of breast malignancy formation and progression; therefore, crystallographic parameters may have a role as prognostic markers in breast cancer.
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    A multi-modal exploration of heterogeneous physico–chemical properties of DCIS breast microcalcifications
    (Royal Society of Chemistry, 2022-03-21) Gosling, Sarah; Calabrese, Doriana; Nallala, Jayakrupakar; Greenwood, Charlene; Pinder, Sarah; King, Lorraine; Marks, Jeffrey; Pinto, Donna; Lynch, Thomas; Lyburn, Iain Douglas; Hwang, Shelley; Grand Challenge PRECISION Consortium; Rogers, Keith; Stone, Nicholas
    Ductal carcinoma in situ (DCIS) is frequently associated with breast calcification. This study combines multiple analytical techniques to investigate the heterogeneity of these calcifications at the micrometre scale. X-ray diffraction, scanning electron microscopy and Raman and Fourier-transform infrared spectroscopy were used to determine the physicochemical and crystallographic properties of type II breast calcifications located in formalin fixed paraffin embedded DCIS breast tissue samples. Multiple calcium phosphate phases were identified across the calcifications, distributed in different patterns. Hydroxyapatite was the dominant mineral, with magnesium whitlockite found at the calcification edge. Amorphous calcium phosphate and octacalcium phosphate were also identified close to the calcification edge at the apparent mineral/matrix barrier. Crystallographic features of hydroxyapatite also varied across the calcifications, with higher crystallinity centrally, and highest carbonate substitution at the calcification edge. Protein was also differentially distributed across the calcification and the surrounding soft tissue, with collagen and β-pleated protein features present to differing extents. Combination of analytical techniques in this study was essential to understand the heterogeneity of breast calcifications and how this may link crystallographic and physicochemical properties of calcifications to the surrounding tissue microenvironment.
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    Thermally dynamic examination of local order in nanocrystalline hydroxyapatite
    (Elsevier, 2022-08-13) Arnold, Emily; Gosling, Sarah; Davies, Samantha K.; Cross, Hannah L.; Evans, Paul; Keeble, Dean S.; Greenwood, Charlene; Rogers, Keith D.
    The main mineral component of bone is hydroxyapatite, a commonly nanocrystalline material which presents many challenges for those trying to characterize it. Here, local structure is analyzed using X-ray total scattering for synthetic samples, to enable a better understanding of the nanocrystalline nature of hydroxyapatite. Two samples were measured dynamically during heat treatment from 25°C to 800°C, and were analyzed using small box modelling. Analysis of sequential measurements when dwelling at key temperatures showed a significant relationship between time and temperature, indicating a process occurring more slowly than thermal expansion. This indicates a decrease in B-type CO32- substitution between 550°C and 575°C and an increase in A-type CO32- substitution above 750°C. A greater understanding of local, intermediate, and long-range order of this complex biomineral during heat treatment can be of interest in several sectors, such as in forensic, biomedical and clinical settings for the study of implant coatings and bone diseases including osteoporosis and osteoarthritis.