I18-Microfocus Spectroscopy
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Sarah B.
Gosling
,
Emily L.
Arnold
,
Lois
Adams
,
Paul
Cool
,
Kalotina
Geraki
,
Mark O.
Kitchen
,
Iain D.
Lyburn
,
Keith D.
Rogers
,
Tim
Snow
,
Nick
Stone
,
Charlene E.
Greenwood
Diamond Proposal Number(s):
[31847]
Open Access
Abstract: Calcifications across the body offer snapshots of the surrounding ionic environment at the time of their formation. Links between prostate calcification chemistry and cancer are becoming of increasing interest, particularly in identifying biomarkers for disease. This study utilizes X-ray fluorescence mapping of 72 human prostate calcifications, measured at the I18 beamline at the Diamond Light Source, to determine the links between calcifications and their environment. This paper offers the first investigation of the elemental heterogeneity of prostate calcifications, demonstrating lower relative levels of minor elements at the calcification center compared to the edge but higher levels of zinc. Importantly, this study uniquely presents links between average Fe, Cr, Mn, Cu, and Ni ratios and grade Group (a classification system for urological tumors, specifically for prostate cancer), highlighting a potential avenue of exploration for biomarkers in prostate calcifications.
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Jul 2025
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I18-Microfocus Spectroscopy
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Sarah B.
Gosling
,
Emily L.
Arnold
,
Lois
Adams
,
Paul
Cool
,
Kalotina
Geraki
,
Mark O.
Kitchen
,
Iain D.
Lyburn
,
Keith D.
Rogers
,
Tim
Snow
,
Nick
Stone
,
Charlene E.
Greenwood
Diamond Proposal Number(s):
[31847]
Open Access
Abstract: Prostate cancer remains the most common male cancer; however, treatment regimens remain unclear in some cases due to a lack of agreement in current testing methods. Therefore, there is an increasing need to identify novel biomarkers to better counsel patients about their treatment options. Microcalcifications offer one such avenue of exploration. Microfocus spectroscopy at the i18 beamline at Diamond Light Source was utilised to measure X-ray diffraction and fluorescence maps of calcifications in 10 µm thick formalin fixed paraffin embedded prostate sections. Calcifications predominantly consisted of hydroxyapatite (HAP) and whitlockite (WH). Kendall’s Tau statistics showed weak correlations of ‘a’ and ‘c’ lattice parameters in HAP with GG (rτ = − 0.323, p = 3.43 × 10–4 and rτ = 0.227, p = 0.011 respectively), and a negative correlation of relative zinc levels in soft tissue (rτ = − 0.240, p = 0.022) with GG. Negative correlations of the HAP ‘a’ axis (rτ = − 0.284, p = 2.17 × 10–3) and WH ‘c’ axis (rτ = − 0.543, p = 2.83 × 10–4) with pathological stage were also demonstrated. Prostate calcification chemistry has been revealed for the first time to correlate with clinical markers, highlighting the potential of calcifications as biomarkers of prostate cancer.
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Apr 2025
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B22-Multimode InfraRed imaging And Microspectroscopy
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Diamond Proposal Number(s):
[27207]
Open Access
Abstract: There is cumulative evidence that lipid metabolism plays a key role in the pathogenesis of various neurodegenerative disorders including Alzheimer’s disease (AD). Visualising lipid content in a non-destructive label-free manner can aid in elucidating the AD phenotypes towards a better understanding of the disease. In this study, we combined multiple optical molecular-specific methods, Fourier transform infrared (FTIR) spectroscopic imaging, synchrotron radiation-infrared (SR-IR) microscopy, Raman and stimulated Raman scattering (SRS) microscopy, and optical-photothermal infrared (O-PTIR) microscopy with multivariate data analysis, to investigate the biochemistry of brain hippocampus in situ using a mouse model of tauopathy (rTg4510). We observed a significant difference in the morphology and lipid content between transgenic (TG) and wild type (WT) samples. Immunohistochemical staining revealed some degree of microglia co-localisation with elevated lipids in the brain. These results provide new evidence of tauopathy-related dysfunction in a preclinical study at a subcellular level.
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Oct 2024
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I18-Microfocus Spectroscopy
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Open Access
Abstract: Rationale and objectives: The potential of breast microcalcification chemistry to provide clinically valuable intelligence is being increasingly studied. However, acquisition of crystallographic details has, to date, been limited to high brightness, synchrotron radiation sources. This study, for the first time, evaluates a laboratory-based system that interrogates histological sections containing microcalcifications. The principal objective was to determine the measurement precision of the laboratory system and assess whether this was sufficient to provide potentially clinical valuable information. Materials and methods: Sections from 5 histological specimens from breast core biopsies obtained to evaluate mammographic calcification were examined using a synchrotron source and a laboratory-based instrument. The samples were chosen to represent a significant proportion of the known breast tissue, mineralogical landscape. Data were subsequently analysed using conventional methods and microcalcification characteristics such as crystallographic phase, chemical deviation from ideal stoichiometry and microstructure were determined. Results: The crystallographic phase of each microcalcification (e.g., hydroxyapatite, whitlockite) was easily determined from the laboratory derived data even when a mixed phase was apparent. Lattice parameter values from the laboratory experiments agreed well with the corresponding synchrotron values and, critically, were determined to precisions that were significantly greater than required for potential clinical exploitation. Conclusion: It has been shown that crystallographic characteristics of microcalcifications can be determined in the laboratory with sufficient precision to have potential clinical value. The work will thus enable exploitation acceleration of these latent microcalcification features as current dependence upon access to limited synchrotron resources is minimized.
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Mar 2024
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I18-Microfocus Spectroscopy
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Sarah B.
Gosling
,
Emily L.
Arnold
,
Samantha K.
Davies
,
Hannah
Cross
,
Ihssane
Bouybayoune
,
Doriana
Calabrese
,
Jayakrupakar
Nallala
,
Sarah E.
Pinder
,
Liping
Fu
,
Esther H.
Lips
,
Lorraine
King
,
Jeffrey
Marks
,
Allison
Hall
,
Lars J.
Grimm
,
Thomas
Lynch
,
Donna
Pinto
,
Hilary
Stobart
,
E. Shelley
Hwang
,
Jelle
Wesseling
,
Kalotina
Geraki
,
Nicholas
Stone
,
Iain D.
Lyburn
,
Charlene
Greenwood
,
Keith D.
Rogers
,
Alastair
Thompson
,
Serena
Nik-Zainal
,
Elinor J.
Sawyer
,
Helen
Davies
,
Andrew
Futreal
,
Nicholas
Navin
,
Jos
Jonkers
,
Jacco
Van Rheenen
,
Fariba
Behbod
,
Marjanka
Schmidt
,
Lodewyk F. A.
Wessels
,
Daniel
Rea
,
Proteeti
Bhattacharjee
,
Deborah
Collyar
,
Ellen
Verschuur
,
Marja
Van Oirsouw
Diamond Proposal Number(s):
[21565, 25414, 27300, 23072]
Open Access
Abstract: Ductal carcinoma in-situ (DCIS) accounts for 20–25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation.
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Jun 2023
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I18-Microfocus Spectroscopy
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Abstract: Prostate cancer is the most common cancer for men in
Europe, accounting for 22 % of all new diagnoses [1].
Diagnosis and prognosis are usually determined with
prostate specific antigen (PSA) testing or MRI and/or
biopsy but results are often conflicting (in 15-20% of
cases), which can lead to over- or undertreatment,
causing increased incontinence, impotence and mortality.
Identifying robust biomarkers in the prostate tissue
microenvironment remains an important investigative
avenue for prostate cancer diagnostics and prognostics.
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Jun 2023
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I18-Microfocus Spectroscopy
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Sarah
Gosling
,
Doriana
Calabrese
,
Jayakrupakar
Nallala
,
Charlene
Greenwood
,
Sarah
Pinder
,
Lorraine
King
,
Jeffrey
Marks
,
Donna
Pinto
,
Thomas
Lynch
,
Iain D.
Lyburn
,
E. Shelley
Hwang
,
Cruk
Grand Challenge Precision Consortium
,
Keith
Rogers
,
Nicholas
Stone
Diamond Proposal Number(s):
[21565, 25414, 27300]
Open Access
Abstract: 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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Mar 2022
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I18-Microfocus Spectroscopy
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Open Access
Abstract: Background/Introduction: Breast microcalcifications are deposits of calcium oxalate, found mostly in benign tissue, or calcium phosphate in the form of hydroxyapatite, found in benign and malignant tissue. Differences in the crystallographic properties and chemical make-up of hydroxyapatite breast microcalcifications have previously been noted in differing breast pathologies.
Purpose: Ductal carcinoma in-situ (DCIS) is a precancerous breast lesion, which has the potential to form invasive breast cancer. Currently there are no definitive markers to determine DCIS invasiveness, therefore this work aims to elucidate differences in the calcification chemistry between invasive and non-invasive cases of DCIS, ultimately developing a novel biomarker for DCIS progression.
Methods: 75 formalin fixed paraffin embedded archive breast tissue samples were used subject to NHS REC approval (ref. 18/LO/0945). X-ray diffraction was carried out at 12keV on beamline i18 at Diamond Light Source, UK to determine crystallographic properties of 279 breast calcifications. SEM-EDS experiments were carried out on a Hitachi SU3500 at 11kV under low vacuum.
Results: Significant differences (P < 0.05) were observed in the proportion of magnesium whitlockite found as a secondary phase in breast calcifications from invasive (3.51 %) and non-invasive (2.82 %) DCIS samples. Additionally, crystallographic features of hydroxyapatite, the bulk of calcifications in both cases, were found to differ between the two groups. The d-spacing between crystallographic planes, was significantly (P < 0.001) larger in invasive compared to non-invasive DCIS cases. Finally, the calcium to phosphate ratio measured using EDS was significantly lower (P < 0.001) in invasive samples (1.60) compared to non-invasive samples (1.67), which more closely reflected stoichiometric hydroxyapatite.
Conclusion(s): Differences in calcification chemistry and crystallographic structure between invasive and non-invasive DCIS cases have been demonstrated in this study. Therefore, calcification chemistry is a key candidate for novel DCIS progression biomarkers and could ultimately lower treatment expenditure and improve patient quality of life by reducing overtreatment.
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May 2021
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I18-Microfocus Spectroscopy
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Diamond Proposal Number(s):
[12303]
Open Access
Abstract: 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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Dec 2019
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I18-Microfocus Spectroscopy
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Diamond Proposal Number(s):
[12303]
Open Access
Abstract: Calcifications are not only one of the most important early diagnostic markers of breast cancer, but are also increasingly believed to aggravate the proliferation of cancer cells and invasion of surrounding tissue. Moreover, this influence appears to vary with calcification composition. Despite this, remarkably little is known about the composition and crystal structure of the most common type of breast calcifications, and how this differs between benign and malignant lesions. We sought to determine how the phase composition and crystallographic parameters within calcifications varies with pathology, using synchrotron X-ray diffraction. This is the first time crystallite size and lattice parameters have been measured in breast calcifications, and we found that these both parallel closely the changes in these parameters with age observed in fetal bone. We also discovered that these calcifications contain a small proportion of magnesium whitlockite, and that this proportion increases from benign to in situ to invasive cancer. When combined with other recent evidence on the effect of magnesium on hydroxyapatite precipitation, this suggests a mechanism explaining observations that carbonate levels within breast calcifications are lower in malignant specimens.
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Sep 2016
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