Kendall, Catherine
Loading...
Biography
I am a Clinical Scientist, scientific lead for the Biophotonics Research Unit & Head of Diagnostic Radiology physics. The Biophotonics Research Unit's goals are to pioneer the field of novel optical diagnostics within the clinical environment.
My research focuses on the use of light to improve cancer diagnostics using a technique called Raman spectroscopy. This has moved on from proof-of-concept studies completed during my PhD at GHs/Cranfield University to recent NIHR i4i funded clinical trials including DOLPHIN-vivo (Diagnosis of LymPHoma IN VIVO) and RAPIDE (RAman Probe for In vivo Diagnostics (during oesophageal) Endoscopy) in collaboration with the Universities of Bristol and Exeter.
In 2024 I received the NHS England SW Healthcare Science Award for Innovation Excellence.
14 results
Publication Search Results
Now showing 1 - 10 of 14
Publication Fiber optic Raman spectroscopy for the evaluation of disease state in Duchenne muscular dystrophy: An assessment using the mdx model and human muscle(Wiley, 2022-07-15) Alix, James; Plesia, Maria; Hool, Sarah; Coldicott, Ian; Kendall, Catherine; Shaw Dbe, Pamela; Mead, Richard; Day, John; Kendall, Catherine; Healthcare ScientistsIntroduction/aims: Raman spectroscopy is an emerging technique for the evaluation of muscle disease. In this study we evaluate the ability of in vivo intramuscular Raman spectroscopy to detect the effects of voluntary running in the mdx model of Duchenne muscular dystrophy (DMD). We also compare mdx data with muscle spectra from human DMD patients. Methods: Thirty 90-day-old mdx mice were randomly allocated to an exercised group (48-hour access to a running wheel) and an unexercised group (n = 15 per group). In vivo Raman spectra were collected from both gastrocnemius muscles and histopathological assessment subsequently performed. Raman data were analyzed using principal component analysis-fed linear discriminant analysis (PCA-LDA). Exercised and unexercised mdx muscle spectra were compared with human DMD samples using cosine similarity. Results: Exercised mice ran an average of 6.5 km over 48 hours, which induced a significant increase in muscle necrosis (P = .03). PCA-LDA scores were significantly different between the exercised and unexercised groups (P < .0001) and correlated significantly with distance run (P = .01). Raman spectra from exercised mice more closely resembled human spectra than those from unexercised mice. Discussion: Raman spectroscopy provides a readout of the biochemical alterations in muscle in both the mdx mouse and human DMD muscle.Publication Use of routinely collected health data in randomised clinical trials: comparison of trial-specific death data in the BOSS trial with NHS Digital data(Biomed Central, 2021-09-26) Love, Sharon; Kilanowski, Anna; Yorke-Edwards, Victoria; Old, Oliver; Barr, Hugh; Stokes, Clive; Kendall, Catherine; Sydes, Matthew; Old, Oliver; Barr, Hugh; Stokes, Clive; Kendall, Catherine; Medical and Dental; Healthcare Scientists; Admin and ClericalBackground: A promising approach to reduce the increasing costs of clinical trials is the use of routinely collected health data as participant data. However, the quality of this data could limit its usability as trial participant data. Methods: The BOSS trial is a randomised controlled trial comparing regular endoscopies versus endoscopies at need in patients with Barrett's oesophagus with primary endpoint death. Data on death and cancer collected every 2 years after randomisation (trial-specific data) were compared to data received annually (all patients on one date) from the routinely collected health data source National Health Service (NHS) Digital. We investigated completeness, agreement and timeliness and looked at the implications for the primary trial outcome. Completeness and agreement were assessed by evaluating the number of reported and missing cases and any disparities between reported dates. Timeliness was considered by graphing the year a death was first reported in the trial-specific data against that for NHS Digital data. Implications on the primary trial outcome, overall survival, of using one of the data sources alone were investigated using Kaplan-Meier graphs. To assess the utility of cause of death and cancer diagnoses, oesophageal cancer cases were compared. Results: NHS Digital datasets included more deaths and often reported them sooner than the trial-specific data. The number reported as being from oesophageal cancer was similar in both datasets. Due to time lag in reporting and missing cases, the event rate appeared higher using the NHS Digital data. Conclusion: NHS Digital death data is useful for calculating overall survival where trial-specific follow-up is only every 2 years from randomisation and the follow-up requires patient response. The cancer data was not a large enough sample to assess usability. We suggest that this assessment of registry data is done for more phase III RCTs and for more registry data to get a more complete picture of when RCHD would be useful in phase III RCT.Publication Conformational fingerprinting with Raman spectroscopy reveals protein structure as a translational biomarker of muscle pathology(Royal Society of Chemistry, 2024-03-27) Alix, James; Plesia, Maria; Dudgeon, Alexander; Kendall, Catherine; Hewamadduma, Channa; Hadjivassiliou, Marios; Gorman, Gráinne; Taylor, Robert; McDermott, Christopher; Shaw, Pamela; Mead, Richard; Day, John; Dudgeon, Alexander; Kendall, Catherine; Healthcare ScientistsNeuromuscular disorders are a group of conditions that can result in weakness of skeletal muscles. Examples include fatal diseases such as amyotrophic lateral sclerosis and conditions associated with high morbidity such as myopathies (muscle diseases). Many of these disorders are known to have abnormal protein folding and protein aggregates. Thus, easy to apply methods for the detection of such changes may prove useful diagnostic biomarkers. Raman spectroscopy has shown early promise in the detection of muscle pathology in neuromuscular disorders and is well suited to characterising the conformational profiles relating to protein secondary structure. In this work, we assess if Raman spectroscopy can detect differences in protein structure in muscle in the setting of neuromuscular disease. We utilise in vivo Raman spectroscopy measurements from preclinical models of amyotrophic lateral sclerosis and the myopathy Duchenne muscular dystrophy, together with ex vivo measurements of human muscle samples from individuals with and without myopathy. Using quantitative conformation profiling and matrix factorisation we demonstrate that quantitative 'conformational fingerprinting' can be used to identify changes in protein folding in muscle. Notably, myopathic conditions in both preclinical models and human samples manifested a significant reduction in α-helix structures, with concomitant increases in β-sheet and, to a lesser extent, nonregular configurations. Spectral patterns derived through non-negative matrix factorisation were able to identify myopathy with a high accuracy (79% in mouse, 78% in human tissue). This work demonstrates the potential of conformational fingerprinting as an interpretable biomarker for neuromuscular disorders.Publication The application of Raman spectroscopy to the diagnosis of mitochondrial muscle disease: A preliminary comparison between fibre optic probe and microscope formats(Wiley, 2021-11-02) Alix, James; Plesia, Maria; Lloyd, Gavin; Dudgeon, Alexander; Kendall, Catherine; McDermott, Christopher; Gorman, Grainne; Taylor, Robert; Shaw, Pamela; Day, John; Dudgeon, Alexander; Kendall, Catherine; Healthcare ScientistsMuscle biopsy remains an important component of the diagnostic repertoire for patients with suspected mitochondrial disease, underpinning specialist histopathological and biochemical analyses. Raman spectroscopy has not yet been applied to mitochondrial disease, and new fibre optic systems, with advantages in terms of cost and portability, could provide a rapid means to identify muscle pathology. In this study, we aimed to explore the potential of two different formats of Raman spectroscopy to identify mitochondrial disease: a miniaturised fibre optic Raman system and a standard commercial Raman microscope. Raman spectra were recorded from muscle samples from healthy volunteers (n = 10) and patients with genetically confirmed mitochondrial disease (n = 15). Multivariate classification algorithms demonstrated a high level of disease classification performance with both the fibre optic probe system and microscope (area under receiver operating characteristic curves 0.80–0.82). Key spectral changes associated with mitochondrial disease concerned the α-helical configuration of proteins. The results suggest that Raman spectroscopy of muscle is worthy of further investigation as a technique for the rapid identification of mitochondrial disease. Open ResearchPublication Optimising Shifted Excitation Raman Difference Spectroscopy (SERDS) for application in highly fluorescent biological samples, using fibre optic probes(Royal Society of Chemistry, 2024-11-19) Sheridan, Hannah; Dudgeon, Alexander; Day, John; Kendall, Catherine; Hall, Charlie; Stone, Nick; Dudgeon, Alexander; Kendall, Catherine; Hall, Charlie; Stone, Nick; Healthcare Scientists; Medical and DentalFibre optic probe based Raman spectroscopy can deliver in vivo molecular compositional analysis of a range of diseases. However, some biological tissues exhibit high levels of fluorescence which limit the utility of the technique, particularly when the fluorescence induces CCD etaloning, which can be particulalry hard to remove in subsequent analysis. Furthermore, use of fibre probes can result in silica signals superimposed on the biological Raman signals. Shifted excitation Raman difference spectroscopy (SERDS) utilises a small seperation in excitation wavelengths to remove signals from fluorescence, room lights, optical components and etaloning contributions, while retaining chemical signals from the sample. In this study, we sought to measure the optimum SERDS spectra enabling reconstruction of a range a narrow and broad peaks found in biological samples. A original wavelength of 830 nm was utilised with 7 different shifts between 0.4 and 3.9 nm to determine which gave the best performance. This range roughly corresponds to the typical range of peak widths within biological Raman spectra at 830 nm excitation; 0.41 – 3.25 nm or 6 – 47 cm−1. An wavelength shift of 2.4 nm was identified as optimal. Finally, a fibre optic Raman probe was used to measure 2 human lymph nodes ex vivo to demonstrate the feasibility of the approach with real-world examples.Publication Non-negative matrix factorisation of Raman spectra finds common patterns relating to neuromuscular disease across differing equipment configurations, preclinical models and human tissue(Wiley, 2022-12-22) Alix, James; Plesia, Maria; Schooling, Chloe; Dudgeon, Alexander; Kendall, Catherine; Kadirkamanathan, Visakan; McDermott, Christopher; Gorman, Grainne; Taylor, Robert; Mead, Richard; Shaw, Pamela; Day, John; Dudgeon, Alexander; Kendall, Catherine; Healthcare ScientistsRaman spectroscopy shows promise as a biomarker for complex nerve and muscle (neuromuscular) diseases. To maximise its potential, several challenges remain. These include the sensitivity to different instrument configurations, translation across preclinical/human tissues and the development of multivariate analytics that can derive interpretable spectral outputs for disease identification. Nonnegative matrix factorisation (NMF) can extract features from high-dimensional data sets and the nonnegative constraint results in physically realistic outputs. In this study, we have undertaken NMF on Raman spectra of muscle obtained from different clinical and preclinical settings. First, we obtained and combined Raman spectra from human patients with mitochondrial disease and healthy volunteers, using both a commercial microscope and in-house fibre optic probe. NMF was applied across all data, and spectral patterns common to both equipment configurations were identified. Linear discriminant models utilising these patterns were able to accurately classify disease states (accuracy 70.2-84.5%). Next, we applied NMF to spectra obtained from the mdx mouse model of a Duchenne muscular dystrophy and patients with dystrophic muscle conditions. Spectral fingerprints common to mouse/human were obtained and able to accurately identify disease (accuracy 79.5-98.8%). We conclude that NMF can be used to analyse Raman data across different equipment configurations and the preclinical/clinical divide. Thus, the application of NMF decomposition methods could enhance the potential of Raman spectroscopy for the study of fatal neuromuscular diseases.Publication Barrett’s Oesophagus Surveillance Versus Endoscopy at Need Study (BOSS): A Randomized Controlled Trial(Elsevier, 2025-04-01) Old, Oliver; Jankowski, Janusz; Attwood, Stephen; Stokes, Clive; Kendall, Catherine; Rasdell, Cathryn; Zimmermann, Alex; Massa, Maria; Love, Sharon; Sanders, Scott; Deidda, Manuela; Briggs, Andrew; Hapeshi, Julie; Foy, Chris; Moayyedi, Paul; Barr, Hugh; Old, Oliver; Stokes, Clive; Kendall, Catherine; Rasdell, Cathryn; Hapeshi, Julie; Foy, Chris; Barr, Hugh; Medical and Dental; Admin and Clerical; Healthcare ScientistsBackground & Aims Barrett’s esophagus (BE) is a precursor lesion for esophageal adenocarcinoma (EAC). Surveillance endoscopy aims to detect early malignant progression; although widely practiced, it has not previously been tested in a randomized trial. Methods BOSS (Barrett’s Oesophagus Surveillance Versus Endoscopy at Need Study) was a randomized controlled trial at 109 centers in the United Kingdom. Patients with BE were randomized to 2-yearly surveillance endoscopy or “at-need” endoscopy, offered for symptoms only. Follow-up was a minimum of 10 years. The primary outcome was overall survival in the intention-to-treat population. Secondary outcomes included cancer-specific survival, time to diagnosis of EAC, stage of EAC at diagnosis, frequency of endoscopy, and serious adverse events related to interventions. Results There were 3453 patients recruited; 1733 patients were randomized to surveillance and 1719 to at-need endoscopy. Median follow-up time was 12.8 years for the primary outcome. There was no evidence of a difference in overall survival between the surveillance arm (333 deaths among 1733 patients) and the at-need arm (356 deaths among 1719 patients; hazard ratio, 0.95; 95% CI, 0.82–1.10; stratified log-rank P = .503). There was no evidence of a difference for surveillance vs at-need endoscopy in cancer-specific survival (108 vs 106 deaths from any cancer; hazard ratio, 1.01; 95% CI, 0.77–1.33; P = .926), time to diagnosis of EAC (40 vs 31 patients had a diagnosis of EAC; hazard ratio, 1.32; 95% CI, 0.82–2.11; P = .254), or cancer stage at diagnosis. Eight surveillance patients (0.46%) and 7 at-need patients (0.41%) reported serious adverse events. Conclusions Surveillance did not improve overall survival or cancer-specific survival. At-need endoscopy may be a safe alternative for low-risk patients. (ClinicalTrials.gov, Number: NCT00987857.)Publication Cost-Effectiveness of Regular Surveillance Versus Endoscopy at Need for Patients With Barrett’s Esophagus: Economic Evaluation Alongside the Barrett’s Oesophagus Surveillance Study (BOSS) Randomized Controlled Trial(Elsevier, 2025-05-15) Deidda, Manuela; Old, Oliver; Jankowski, Janusz; Attwood, Stephen; Stokes, Clive; Kendall, Catherine; Rasdell, Cathryn; Zimmermann, Alex; Massa, Sofia; Love, Sharon; Hapeshi, Julie; Sanders, Scott; Foy, Chris; Briggs, Andrew; Barr, Hugh; Moayyedi, Paul; Old, Oliver; Stokes, Clive; Kendall, Catherine; Rasdell, Cathryn; Hapeshi, Julie; Foy, Chris; Barr, Hugh; Medical and Dental; Additional Professional Scientific and Technical; Admin and ClericalBackground & aims: The Barrett's Oesophagus Surveillance Study (BOSS) was the first randomized study of surveillance. This study reports the costs and quality of life outcomes from the BOSS trial and models the outcomes and cost-effectiveness of surveillance beyond the follow-up period of the BOSS study. This trial showed similar stages and rates of esophageal cancer in both arms, but the regular surveillance arm did identify more high-grade dysplasia after a median of 12.8 years follow-up. Methods: We used a decision tree model based on results from BOSS to conduct a cost-effectiveness analysis of costs and quality-adjusted life years (QALYs). A Markov model was used to extrapolate costs and outcomes over a further 10 years after the trial had ended, representing a 22.8-year time horizon. The proportion with high-grade dysplasia and QALYs was derived from the randomized trial. Results: The total costs associated with 2-yearly surveillance was $5309 vs $3182 in the at-need arm. Total QALYs in the 2-yearly endoscopy arm were 8.647 compared with 8.629 in the at-need arm. Compared with at-need endoscopy, 2-yearly surveillance costs $115,563/QALY gained. In the sensitivity analyses around assumptions on the proportion of high-grade dysplasia that is undetected in the at-need endoscopy arm, surveillance had an incremental cost effectiveness ratio of $94,513/QALY for the best-case and $146,272/QALY for the worst-case scenario. Conclusion: Barrett's esophagus surveillance every 2 to 3 years is unlikely to be a cost-effective strategy. Guidelines should take this into account when deciding surveillance intervals.Publication Comparability of Raman Spectroscopic Configurations: A Large Scale Cross-Laboratory Study(American Chemical Society, 2020-11-21) Guo, Shuxia; Beleites, Claudia; Neugebauer, Ute; Abalde-Cela, Sara; Afseth, Nils; Alsamad, Fatima; Anand, Suresh; Araujo-Andrade, Cuauhtemoc; Aškrabic, Sonja; Avci, Ertug; Baia, Monica; Kendall, Catherine; Kendall, Catherine; Additional Professional Scientific and TechnicalThe variable configuration of Raman spectroscopic platforms is one of the major obstacles in establishing Raman spectroscopy as a valuable physicochemical method within real-world scenarios such as clinical diagnostics. For such real world applications like diagnostic classification, the models should ideally be usable to predict data from different setups. Whether it is done by training a rugged model with data from many setups or by a primary-replica strategy where models are developed on a ‘primary’ setup and the test data are generated on ‘replicate’ setups, this is only possible if the Raman spectra from different setups are consistent, reproducible, and comparable. However, Raman spectra can be highly sensitive to the measurement conditions, and they change from setup to setup even if the same samples are measured. Although increasingly recognized as an issue, the dependence of the Raman spectra on the instrumental configuration is far from being fully understood and great effort is needed to address the resulting spectral variations and to correct for them. To make the severity of the situation clear, we present a round robin experiment investigating the comparability of 35 Raman spectroscopic devices with different configurations in 15 institutes within seven European countries from the COST (European Cooperation in Science and Technology) action Raman4clinics. The experiment was developed in a fashion that allows various instrumental configurations ranging from highly confocal setups to fibre-optic based systems with different excitation wavelengths. We illustrate the spectral variations caused by the instrumental configurations from the perspectives of peak shifts, intensity variations, peak widths, and noise levels. We conclude this contribution with recommendations that may help to improve the inter-laboratory studies.Publication OGC P28 Raman Needle Probe Lymph Node Assessment for Oesophageal Cancer: The DOLOMITE Study(Oxford University Press, 2022-12-07) Ireland, Philip; Old, Oliver; Hornby, Steve; Kendall, Catherine; Barr, Hugh; Shore, Angela; Stone, Nick; Ireland, Philip; Old, Oliver; Hornby, Steve; Kendall, Catherine; Barr, Hugh; Medical and Dental; Healthcare ScientistsNo abstract available