I22-Small angle scattering & Diffraction
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Sasha
Murokh
,
Alexander
Alekseev
,
Viacheslav
Kubytskyi
,
Viacheslav
Shcherbakov
,
Oleksii
Avdieiev
,
Sergey A.
Denisov
,
Ashkan
Ajeer
,
Lois
Adams
,
Charlene
Greenwood
,
Keith
Rogers
,
Lev
Mourokh
,
Pavel
Lazarev
Diamond Proposal Number(s):
[24977]
Open Access
Abstract: Structural biomarkers determined by X-ray scattering of the tissues can complement conventional histopathology and facilitate a fast triage procedure of cancer biopsy samples. It has been shown previously that lipid reflexes can distinguish cancerous from benign samples, except for fibroadenomas. In the present study, we demonstrate that fibroadenoma samples can be recognized using X-ray scattering of collagen. Moreover, we show that modifications in collagen structure are manifested in the water reflexes. Examination of diffraction patterns from water using two-dimensional Fourier transformation and machine learning yields excellent classification metrics in both synchrotron images and laboratory diffractometer data.
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Feb 2026
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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: 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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I22-Small angle scattering & Diffraction
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Oleksii
Avdieiev
,
Sergey A.
Denisov
,
Ashkan
Ajeer
,
Lois
Adams
,
Charlene
Greenwood
,
Heather
Nesbitt
,
Keith
Thomas
,
Keith
Rogers
,
Olga
Solovyeva
,
Lev
Mourokh
,
Pavel
Lazarev
Open Access
Abstract: Structural biomarkers determined by X-ray scattering of the tissues can complement conventional diagnostics and provide a pathway for early detection of diseases. In the present study, mouse models were utilized to observe the progression of prostate cancer. We induced cancer in the left lobe of the mouse prostate, whilst the right lobe was left uninoculated. The mice were sacrificed at increasing systematic time points, and lobe samples were subsequently analyzed using X-ray scattering. Control samples were also collected from healthy mice sacrificed at the same time points. This investigation revealed that the ratio between the X-ray scattering peaks associated with the lipids and water can serve as a structural biomarker of cancer, and this biomarker develops as the tumor advances. The obtained cancer trajectory can serve as a baseline for the determination of the disease stage, and the biomarker movement along the trajectory can be evidence of the healing or disease progression.
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Jun 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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I18-Microfocus Spectroscopy
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Robert
Scott
,
Iain D.
Lyburn
,
Eleanor
Cornford
,
Pascaline
Bouzy
,
Nicholas
Stone
,
Charlene
Greenwood
,
Sarah
Gosling
,
Emily L.
Arnold
,
Ihsanne
Bouybayoune
,
Sarah E.
Pinder
,
Keith
Rogers
Diamond Proposal Number(s):
[30215]
Open Access
Abstract: X-ray diffraction is widely used to characterise the mineral component of calcified tissue. Broadening of the diffraction peaks yields valuable information on the size of coherently diffracting domains, sometimes loosely described as crystallite size or crystallinity. These domains are markedly anisotropic, hence a single number describing their size is misleading. We present a novel variation on a method for visualising crystallographic anisotropy in X-ray diffraction data. This provides an intuitively interpretable depiction of crystalline domain size and anisotropy. The new method involves creating a polar plot of calculated domain thickness for peaks in a diffractogram versus crystallographic direction. Points with the least error are emphasised. Anisotropic domain dimensions are calculated by refining an ellipsoidal model in a whole pattern fit. These dimensions are then used to overlay an ellipse on the peak broadening plot. This is illustrated by application of the method to calcifications in breast tissue with suspected cancer, which frequently contain whitlockite as well as nanocrystalline apatite. Like most biogenic apatite, this exhibits markedly anisotropic peak broadening. The nature of this anisotropy offers potentially useful information on normal function and pathology of calcified tissue and is a frequently neglected crystallographic feature of these materials.
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Feb 2025
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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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I15-1-X-ray Pair Distribution Function (XPDF)
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Diamond Proposal Number(s):
[24283]
Open Access
Abstract: 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.
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Aug 2022
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I15-1-X-ray Pair Distribution Function (XPDF)
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Diamond Proposal Number(s):
[18638]
Open Access
Abstract: Hydroxyapatite (HA) is a complex material, which is often nanocrystalline when found within a biological setting. This work has directly compared the structural characteristics derived from data collected using a conventional laboratory-based X-ray diffractometer with those collected from a dedicated pair distribution function (PDF) beamline at Diamond Light Source. In particular, the application of PDF analysis methods to carbonated HA is evaluated. 20 synthetic samples were measured using both X-ray diffraction (XRD) and PDFs. Both Rietveld refinement (of laboratory XRD data) and real-space refinement (of PDF data) were used to analyse all samples. The results of Rietveld and real-space refinements were compared to evaluate their application to crystalline and nanocrystalline hydroxyapatite. Significant relationships were observed between real-space refinement parameters and increasing carbonate substitution. Understanding the local order of synthetic hydroxyapatite can benefit several fields, including both biomedical and clinical settings.
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May 2022
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