Publications by authors named "Lesley Honeyfield"

20 Publications

  • Page 1 of 1

Clinical and molecular associations with outcomes at 2 years after acute knee injury: a longitudinal study in the Knee Injury Cohort at the Kennedy (KICK).

Lancet Rheumatol 2021 Sep 24;3(9):e648-e658. Epub 2021 Jun 24.

Centre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, NDORMS, University of Oxford, Oxford, UK.

Background: Joint injury is a major risk factor for osteoarthritis and provides an opportunity to prospectively examine early processes associated with osteoarthritis. We investigated whether predefined baseline demographic and clinical factors, and protein analytes in knee synovial fluid and in plasma or serum, were associated with clinically relevant outcomes at 2 years after knee injury.

Methods: This longitudinal cohort study recruited individuals aged 16-50 years between Nov 1, 2010, and Nov 28, 2014, across six hospitals and clinics in London, UK. Participants were recruited within 8 weeks of having a clinically significant acute knee injury (effusion and structural injury on MRI), which was typically treated surgically. We measured several predefined clinical variables at baseline (eg, time from injury to sampling, extent and type of joint injury, synovial fluid blood staining, presence of effusion, self-reported sex, age, and BMI), and measured 12 synovial fluid and four plasma or serum biomarkers by immunoassay at baseline and 3 months. The primary outcome was Knee Injury and Osteoarthritis Outcome Score (KOOS) at 2 years, adjusted for baseline score, assessed in all patients. Linear and logistic regression models adjusting for predefined covariates were used to assess associations between baseline variables and 2-year KOOS. This study is registered with ClinicalTrials.gov, number NCT02667756.

Findings: We enrolled 150 patients at a median of 17 days (range 1-59, IQR 9-26) after knee injury. 123 (82%) were male, with a median age of 25 years (range 16-50, IQR 21-30). 98 (65%) of 150 participants completed a KOOS at 2 (or 3) years after enrolment (50 participants were lost to follow-up and two were withdrawn due to adverse events unrelated to study participation); 77 (51%) participants had all necessary variables available and were included in the core variable adjusted analysis. In the 2-year dataset mean KOOS improved from 38 (SD 18) at baseline to 79 (18) at 2 years. Baseline KOOS medium-to-large knee effusion, and moderate-to-severe synovial blood staining and their interaction significantly predicted 2-year KOOS (n=77; coefficient -20·5, 95% CI -34·8 to -6·18; p=0·0060). The only predefined biomarkers that showed independent associations with 2-year KOOS were synovial fluid MCP-1 (n=77; -0·015, 0·027 to -0·004 per change in 1 pg/mL units; p=0·011) and IL-6 (n=77; -0·0005, -0·0009 to -0·0001 per change in 1 pg/mL units; p=0·017). These biomarkers, combined with the interaction of effusion and blood staining, accounted for 39% of outcome variability. Two adverse events occurred that were linked to study participation, both at the time of blood sampling (one presyncopal episode, one tenderness and pain at the site of venepuncture).

Interpretation: The combination of effusion and haemarthrosis was significantly associated with symptomatic outcomes after acute knee injury. The synovial fluid molecular protein response to acute knee injury (best represented by MCP-1 and IL-6) was independently associated with symptomatic outcomes but not with structural outcomes, with the biomarkers overall playing a minor role relative to clinical predictors. The relationship between symptoms and structure after acute knee injury and their apparent dissociation early in this process need to be better understood to make clinical progress.

Funding: Versus Arthritis, Kennedy Trust for Rheumatology Research, and NIHR Oxford Biomedical Research Centre.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2665-9913(21)00116-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390381PMC
September 2021

Imaging and Tissue Biomarkers of Choline Metabolism in Diffuse Adult Glioma: 18F-Fluoromethylcholine PET/CT, Magnetic Resonance Spectroscopy, and Choline Kinase α.

Cancers (Basel) 2019 Dec 7;11(12). Epub 2019 Dec 7.

Department of Brain Sciences, Imperial College London, London SW7 2AZ, UK.

The cellular and molecular basis of choline uptake on PET imaging and MRS-visible choline-containing compounds is not well understood. Choline kinase alpha (ChoKα) is an enzyme that phosphorylates choline, an essential step in membrane synthesis. We investigate choline metabolism through 18F-fluoromethylcholine (18F-FMC) PET, MRS, and tissue ChoKα in human glioma. Fourteen patients with a suspected diffuse glioma underwent multimodal 3T MRI and dynamic 18F-FMC PET/CT prior to surgery. Co-registered PET and MRI data were used to target biopsies to regions of high and low choline signal, and immunohistochemistry for ChoKα expression was performed. The 18F-FMC/PET differentiated WHO (World Health Organization) grade IV from grade II and III tumours, whereas MRS differentiated grade III/IV from grade II tumours. Tumoural 18F-FMC/PET uptake was higher than in normal-appearing white matter across all grades and markedly elevated within regions of contrast enhancement. The 18F-FMC/PET correlated weakly with MRS Cho ratios. ChoKα expression on IHC was negative or weak in all but one glioblastoma sample, and did not correlate with tumour grade or imaging choline markers. MRS and 18F-FMC/PET provide complimentary information on glioma choline metabolism. Tracer uptake is, however, potentially confounded by blood-brain barrier permeability. ChoKα overexpression does not appear to be a common feature in diffuse glioma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers11121969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966628PMC
December 2019

Reliability of dynamic contrast-enhanced magnetic resonance imaging data in primary brain tumours: a comparison of Tofts and shutter speed models.

Neuroradiology 2019 Dec 7;61(12):1375-1386. Epub 2019 Aug 7.

Department of Surgery and Cancer, GN1 Commonwealth building, Hammersmith Hospital, Imperial College London, Du Cane Road, London, W12 0NN, UK.

Purpose: The purpose of this study is to investigate the robustness of pharmacokinetic modelling of DCE-MRI brain tumour data and to ascertain reliable perfusion parameters through a model selection process and a stability test.

Methods: DCE-MRI data of 14 patients with primary brain tumours were analysed using the Tofts model (TM), the extended Tofts model (ETM), the shutter speed model (SSM) and the extended shutter speed model (ESSM). A no-effect model (NEM) was implemented to assess overfitting of data by the other models. For each lesion, the Akaike Information Criteria (AIC) was used to build a 3D model selection map. The variability of each pharmacokinetic parameter extracted from this map was assessed with a noise propagation procedure, resulting in voxel-wise distributions of the coefficient of variation (CV).

Results: The model selection map over all patients showed NEM had the best fit in 35.5% of voxels, followed by ETM (32%), TM (28.2%), SSM (4.3%) and ESSM (< 0.1%). In analysing the reliability of K, when considering regions with a CV < 20%, ≈ 25% of voxels were found to be stable across all patients. The remaining 75% of voxels were considered unreliable.

Conclusions: The majority of studies quantifying DCE-MRI data in brain tumours only consider a single model and whole tumour statistics for the output parameters. Appropriate model selection, considering tissue biology and its effects on blood brain barrier permeability and exchange conditions, together with an analysis on the reliability and stability of the calculated parameters, is critical in processing robust brain tumour DCE-MRI data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00234-019-02265-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848046PMC
December 2019

An MRS- and PET-guided biopsy tool for intraoperative neuronavigational systems.

J Neurosurg 2017 Mar 17:1-7. Epub 2017 Mar 17.

Departments of 1 Imaging and.

OBJECTIVE Glioma heterogeneity and the limitations of conventional structural MRI for identifying aggressive tumor components can limit the reliability of stereotactic biopsy and, hence, tumor characterization, which is a hurdle for developing and selecting effective treatment strategies. In vivo MR spectroscopy (MRS) and PET enable noninvasive imaging of cellular metabolism relevant to proliferation and can detect regions of more highly active tumor. Here, the authors integrated presurgical PET and MRS with intraoperative neuronavigation to guide surgical biopsy and tumor sampling of brain gliomas with the aim of improving intraoperative tumor-tissue characterization and imaging biomarker validation. METHODS A novel intraoperative neuronavigation tool was developed as part of a study that aimed to sample high-choline tumor components identified by multivoxel MRS and F-methylcholine PET-CT. Spatially coregistered PET and MRS data were integrated into structural data sets and loaded onto an intraoperative neuronavigation system. High and low choline uptake/metabolite regions were represented as color-coded hollow spheres for targeted stereotactic biopsy and tumor sampling. RESULTS The neurosurgeons found the 3D spherical targets readily identifiable on the interactive neuronavigation system. In one case, areas of high mitotic activity were identified on the basis of high F-methylcholine uptake and elevated choline ratios found with MRS in an otherwise low-grade tumor, which revealed the possible use of this technique for tumor characterization. CONCLUSIONS These PET and MRI data can be combined and represented usefully for the surgeon in neuronavigation systems. This method enables neurosurgeons to sample tumor regions based on physiological and molecular imaging markers. The technique was applied for characterizing choline metabolism using MRS and F PET; however, this approach provides proof of principle for using different radionuclide tracers and other MRI methods, such as MR perfusion and diffusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2016.7.JNS16106.testDOI Listing
March 2017

Analysis of ageing-associated grey matter volume in patients with multiple sclerosis shows excess atrophy in subcortical regions.

Neuroimage Clin 2017 9;13:9-15. Epub 2016 Nov 9.

Division of Brain Sciences, Imperial College London, UK; Centre for Clinical Brain Sciences, University of Edinburgh, UK.

Age of onset in multiple sclerosis (MS) exerts an influence on the course of disease. This study examined whether global and regional brain volumes differed between "younger" and "older" onset MS subjects who were matched for short disease duration, mean 1.9 years and burden as measured by the MS Severity Score and relapses. 21 younger-onset MS subjects (age 30.4 ± 3.2 years) were compared with 17 older-onset (age 48.7 ± 3.3 years) as well as age-matched controls ( = 31, 31.9 ± 3.5 years and  = 21, 47.3 ± 4.0 years). All subjects underwent 3D volumetric T1 and T2-FLAIR imaging. White matter (WM) and grey matter (GM) lesions were outlined manually. Lesions were filled prior to tissue and structural segmentation to reduce classification errors. Volume loss versus control was predominantly in the subcortical GM, at > 13% loss. Younger and older-onset MS subjects had similar, strong excess loss in the putamen, thalamus, and nucleus accumbens. No excess loss was detected in the amygdala or pallidum. The hippocampus and caudate showed significant excess loss in the younger group ( < 0.001) and a strong trend in the older-onset group. These results provide a potential imaging correlate of published neuropsychological studies that reported the association of younger age at disease onset with impaired cognitive performance, including decreased working memory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2016.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121150PMC
November 2017

An MRS- and PET-guided biopsy tool for intraoperative neuronavigational systems.

J Neurosurg 2017 Oct 11;127(4):812-818. Epub 2016 Nov 11.

Departments of 1 Imaging and.

OBJECTIVE Glioma heterogeneity and the limitations of conventional structural MRI for identifying aggressive tumor components can limit the reliability of stereotactic biopsy and, hence, tumor characterization, which is a hurdle for developing and selecting effective treatment strategies. In vivo MR spectroscopy (MRS) and PET enable noninvasive imaging of cellular metabolism relevant to proliferation and can detect regions of more highly active tumor. Here, the authors integrated presurgical PET and MRS with intraoperative neuronavigation to guide surgical biopsy and tumor sampling of brain gliomas with the aim of improving intraoperative tumor-tissue characterization and imaging biomarker validation. METHODS A novel intraoperative neuronavigation tool was developed as part of a study that aimed to sample high-choline tumor components identified by multivoxel MRS and F-methylcholine PET-CT. Spatially coregistered PET and MRS data were integrated into structural data sets and loaded onto an intraoperative neuronavigation system. High and low choline uptake/metabolite regions were represented as color-coded hollow spheres for targeted stereotactic biopsy and tumor sampling. RESULTS The neurosurgeons found the 3D spherical targets readily identifiable on the interactive neuronavigation system. In one case, areas of high mitotic activity were identified on the basis of high F-methylcholine uptake and elevated choline ratios found with MRS in an otherwise low-grade tumor, which revealed the possible use of this technique for tumor characterization. CONCLUSIONS These PET and MRI data can be combined and represented usefully for the surgeon in neuronavigation systems. This method enables neurosurgeons to sample tumor regions based on physiological and molecular imaging markers. The technique was applied for characterizing choline metabolism using MRS and F PET; however, this approach provides proof of principle for using different radionuclide tracers and other MRI methods, such as MR perfusion and diffusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2016.7.JNS16106DOI Listing
October 2017

Disconnection between the default mode network and medial temporal lobes in post-traumatic amnesia.

Brain 2016 12 22;139(Pt 12):3137-3150. Epub 2016 Oct 22.

1 Computational, Cognitive and Clinical Neuroimaging Laboratory, Imperial College London, Division of Brain Sciences, Hammersmith Hospital, London, UK

SEE BIGLER DOI101093/AWW277 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Post-traumatic amnesia is very common immediately after traumatic brain injury. It is characterized by a confused, agitated state and a pronounced inability to encode new memories and sustain attention. Clinically, post-traumatic amnesia is an important predictor of functional outcome. However, despite its prevalence and functional importance, the pathophysiology of post-traumatic amnesia is not understood. Memory processing relies on limbic structures such as the hippocampus, parahippocampus and parts of the cingulate cortex. These structures are connected within an intrinsic connectivity network, the default mode network. Interactions within the default mode network can be assessed using resting state functional magnetic resonance imaging, which can be acquired in confused patients unable to perform tasks in the scanner. Here we used this approach to test the hypothesis that the mnemonic symptoms of post-traumatic amnesia are caused by functional disconnection within the default mode network. We assessed whether the hippocampus and parahippocampus showed evidence of transient disconnection from cortical brain regions involved in memory processing. Nineteen patients with traumatic brain injury were classified into post-traumatic amnesia and traumatic brain injury control groups, based on their performance on a paired associates learning task. Cognitive function was also assessed with a detailed neuropsychological test battery. Functional interactions between brain regions were investigated using resting-state functional magnetic resonance imaging. Together with impairments in associative memory, patients in post-traumatic amnesia demonstrated impairments in information processing speed and spatial working memory. Patients in post-traumatic amnesia showed abnormal functional connectivity between the parahippocampal gyrus and posterior cingulate cortex. The strength of this functional connection correlated with both associative memory and information processing speed and normalized when these functions improved. We have previously shown abnormally high posterior cingulate cortex connectivity in the chronic phase after traumatic brain injury, and this abnormality was also observed in patients with post-traumatic amnesia. Patients with post-traumatic amnesia showed evidence of widespread traumatic axonal injury measured using diffusion magnetic resonance imaging. This change was more marked within the cingulum bundle, the tract connecting the parahippocampal gyrus to the posterior cingulate cortex. These findings provide novel insights into the pathophysiology of post-traumatic amnesia and evidence that memory impairment acutely after traumatic brain injury results from altered parahippocampal functional connectivity, perhaps secondary to the effects of axonal injury on white matter tracts connecting limbic structures involved in memory processing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/aww241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382939PMC
December 2016

A Randomised Comparison Evaluating Changes in Bone Mineral Density in Advanced Prostate Cancer: Luteinising Hormone-releasing Hormone Agonists Versus Transdermal Oestradiol.

Eur Urol 2016 06 17;69(6):1016-25. Epub 2015 Dec 17.

Imperial College Healthcare NHS Trust, London, UK; Imperial College London, London, UK.

Background: Luteinising hormone-releasing hormone agonists (LHRHa), used as androgen deprivation therapy (ADT) in prostate cancer (PCa) management, reduce serum oestradiol as well as testosterone, causing bone mineral density (BMD) loss. Transdermal oestradiol is a potential alternative to LHRHa.

Objective: To compare BMD change in men receiving either LHRHa or oestradiol patches (OP).

Design, Setting, And Participants: Men with locally advanced or metastatic PCa participating in the randomised UK Prostate Adenocarcinoma TransCutaneous Hormones (PATCH) trial (allocation ratio of 1:2 for LHRHa:OP, 2006-2011; 1:1, thereafter) were recruited into a BMD study (2006-2012). Dual-energy x-ray absorptiometry scans were performed at baseline, 1 yr, and 2 yr.

Interventions: LHRHa as per local practice, OP (FemSeven 100μg/24h patches).

Outcome Measurements And Statistical Analysis: The primary outcome was 1-yr change in lumbar spine (LS) BMD from baseline compared between randomised arms using analysis of covariance.

Results And Limitations: A total of 74 eligible men (LHRHa 28, OP 46) participated from seven centres. Baseline clinical characteristics and 3-mo castration rates (testosterone ≤1.7 nmol/l, LHRHa 96% [26 of 27], OP 96% [43 of 45]) were similar between arms. Mean 1-yr change in LS BMD was -0.021g/cm(3) for patients randomised to the LHRHa arm (mean percentage change -1.4%) and +0.069g/cm(3) for the OP arm (+6.0%; p<0.001). Similar patterns were seen in hip and total body measurements. The largest difference between arms was at 2 yr for those remaining on allocated treatment only: LS BMD mean percentage change LHRHa -3.0% and OP +7.9% (p<0.001).

Conclusions: Transdermal oestradiol as a single agent produces castration levels of testosterone while mitigating BMD loss. These early data provide further supporting evidence for the ongoing phase 3 trial.

Patient Summary: This study found that prostate cancer patients treated with transdermal oestradiol for hormonal therapy did not experience the loss in bone mineral density seen with luteinising hormone-releasing hormone agonists. Other clinical outcomes for this treatment approach are being evaluated in the ongoing PATCH trial.

Trial Registration: ISRCTN70406718, PATCH trial (ClinicalTrials.gov NCT00303784).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eururo.2015.11.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854173PMC
June 2016

Contemporary hormone therapy with LHRH agonists for prostate cancer: avoiding osteoporosis and fracture.

Cent European J Urol 2015 20;68(2):165-8. Epub 2015 Apr 20.

Department of Surgery and Cancer, Imperial College, London.

Introduction: Prostate cancer is a large clinical burden across Europe. It is, in fact, the most common cancer in males, accounting for more than 92,300 deaths annually throughout the continent. Prostate cancer is androgen-sensitive; thus an androgen deprivation therapy (ADT) is often used for treatment by reducing androgen to castrate levels. Several ADT agents have achieved benefits with effective palliation, but, unfortunately, severe adverse events are frequent. Contemporary ADT (Luteinising Hormone Releasing Hormone agonist - LHRHa injections) can result in side effects that include osteoporosis and fractures, compromising quality of life and survival.

Methods: In this review we analysed the associated bone toxicity consequent upon contemporary ADT and based on the literature and our own experience we present future perspectives that seek to mitigate this associated toxicity both by development of novel therapies and by better identification and prediction of fracture risk.

Results: Preliminary results indicate that parenteral oestrogen can mitigate associated osteoporotic risk and that CT scans could provide a more accurate indicator of overall bone quality and hence fracture risk.

Conclusions: As healthcare costs increase globally, cheap and effective alternatives that achieve ADT, but mitigate or avoid such bone toxicities, will be needed. More so, innovative techniques to improve both the measurement and the extent of this toxicity, by assessing bone health and prediction of fracture risk, are also required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5173/ceju.2015.513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526606PMC
August 2015

Apparent Diffusion Coefficient of Normal Abdominal Organs and Bone Marrow From Whole-Body DWI at 1.5 T: The Effect of Sex and Age.

AJR Am J Roentgenol 2015 Aug;205(2):242-50

1 Department of Surgery and Cancer, Comprehensive Cancer Imaging Centre, Imperial College, Hammersmith Campus, DuCane Rd, London W12 0NN, UK.

Objective: The objectives of this study were to define the range of apparent diffusion coefficients (ADCs) from whole-body DWI in normal abdominal organs and bone marrow, to identify ADC differences between sexes and changes occurring with age, and to evaluate the effect of the fat fraction (FF) on the ADC of normal liver parenchyma and bone marrow.

Materials And Methods: Fifty-one healthy volunteers (mean age = 38 years; age range = 23-68 years) underwent whole-body DWI using single-shot echo-planar imaging (b = 0, 150, 400, 750, and 1000 s/mm(2)). A two-point Dixon technique was used to evaluate the FF. Perfusion-sensitive ADCs, which we refer to as "ADCALL," and perfusion-insensitive ADCs, which we refer to as "ADCHIGH," of the liver and renal parenchyma, spleen, pancreatic tail, and red and yellow bone marrow were calculated. The relationships between ADC and sex, age, and FF were examined.

Results: ADCALL and ADCHIGH were significantly higher in female volunteers for the pancreatic tail (p = 0.046 and 0.008, respectively), red bone marrow (p = 0.029 and 0.001), and yellow bone marrow (p < 0.001 for both) but with considerable overlap. There were significant negative correlations between ADCALL and ADCHIGH and age in the liver parenchyma (p = 0.008 and 0.01, respectively) and in the yellow bone marrow (p = 0.013 and 0.039) for all subjects. ADCALL and ADCHIGH were also negatively correlated with FF in the liver parenchyma (p = 0.006 and 0.008, respectively) and in yellow bone marrow (p < 0.001 and p = 0.001) in all subjects.

Conclusion: The ADCs of normal liver parenchyma and bone marrow change significantly with age. The ADCs of bone marrow in women are significantly higher than those of men and correlate strongly with FF. These effects may have an impact on image interpretation when using whole-body DWI to assess disease burden and treatment response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2214/AJR.14.13964DOI Listing
August 2015

Night-time immobilization of the distal interphalangeal joint reduces pain and extension deformity in hand osteoarthritis.

Rheumatology (Oxford) 2014 Jun 8;53(6):1142-9. Epub 2014 Feb 8.

Arthritis Research UK Centre for OA Pathogenesis, Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, Rheumatology Department, Therapies Department, Charing Cross Hospital, Imperial College Healthcare NHS Trust, Centre for Haematology, Hammersmith Hospital, Imperial College London, Imaging Department, Charing Cross Hospital, Imperial College Healthcare NHS Trust and Department of Imaging, King's College Hospital, London, UK.Arthritis Research UK Centre for OA Pathogenesis, Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, Rheumatology Department, Therapies Department, Charing Cross Hospital, Imperial College Healthcare NHS Trust, Centre for Haematology, Hammersmith Hospital, Imperial College London, Imaging Department, Charing Cross Hospital, Imperial College Healthcare NHS Trust and Department of Imaging, King's College Hospital, London, UK.

Objective: DIP joint OA is common but has few cost-effective, evidence-based interventions. Pain and deformity [radial or ulnar deviation of the joint or loss of full extension (extension lag)] frequently lead to functional and cosmetic issues. We investigated whether splinting the DIP joint would improve pain, function and deformity.

Methods: A prospective, radiologist-blinded, non-randomized, internally controlled trial of custom splinting of the DIP joint was carried out. Twenty-six subjects with painful, deforming DIP joint hand OA gave written, informed consent. One intervention joint and one control joint were nominated. A custom gutter splint was worn nightly for 3 months on the intervention joint, with clinical and radiological assessment at baseline, 3 and 6 months. Differences in the change were compared by the Wilcoxon signed rank test.

Results: The median average pain at baseline was similar in the intervention (6/10) and control joints (5/10). Average pain (primary outcome measure) and worst pain in the intervention joint were significantly lower at 3 months compared with baseline (P = 0.002, P = 0.02). Differences between intervention and control joint average pain reached significance at 6 months (P = 0.049). Extension lag deformity was significantly improved in intervention joints at 3 months and in splinted joints compared with matched contralateral joints (P = 0.016).

Conclusion: Short-term night-time DIP joint splinting is a safe, simple treatment modality that reduces DIP joint pain and improves extension of the digit, and does not appear to give rise to non-compliance, increased stiffness or joint restriction.

Trial Registration: clinical trials.gov, http://clinicaltrials.gov, NCT01249391.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/ket455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023558PMC
June 2014

Incremental benefit of computer-aided detection when used as a second and concurrent reader of CT colonographic data: multiobserver study.

Radiology 2011 Feb 17;258(2):469-76. Epub 2010 Nov 17.

Department of Specialist Radiology, University College Hospital, Podium Level 2, 235 Euston Road, London NW1 2BU, England.

Purpose: To quantify the changes in reader performance levels, if any, during interpretation of computed tomographic (CT) colonographic data when a computer-aided detection (CAD) system is used as a second or concurrent reader.

Materials And Methods: After institutional review board approval was obtained, 16 experienced radiologists searched for polyps in 112 patients, 56 of whom had 132 polyps. Each case was interpreted on three separate occasions by using an unassisted (without CAD), second-read CAD, or concurrent CAD reading paradigm. The reading paradigm and case order were randomized, with a minimal interval of 1 month between consecutive interpretations. The readers' findings were compared with the reference-truth interpretation. The mean per-patient sensitivity and mean per-patient specificity with CAD were compared with those achieved with unassisted reading. An increase in per-patient sensitivity was considered to be clinically more important than an equivalent decrease in specificity.

Results: The mean per-patient sensitivity for identification of patients with polyps of any size increased significantly with use of second-read CAD (mean increase, 7.0%; 95% confidence interval [CI]: 4.0%, 9.8%) and concurrent CAD (mean increase, 4.5%; 95% CI: 0.8%, 8.2%). The mean per-patient specificity did not decrease significantly with use of second-read CAD (mean decrease, -2.5%; 95% CI: -5.2%, 0.1%) or concurrent CAD (mean decrease, -2.2%; 95% CI: -4.6%, 0.2%). With analysis restricted to patients with polyps 6 mm or larger, the benefit in sensitivity with second-read CAD remained (mean increase, 7.1%; 95% CI: 3.0%, 11.1%), whereas the increase with concurrent CAD was not significant (mean increase, 4.2%; 95% CI: -0.5%, 8.9%). Use of second-read CAD significantly increased the per-polyp sensitivity for polyps 6 mm or larger (mean increase, 9.0%; 98.3% CI: 4.9%, 12.8%) and polyps 5 mm or smaller (mean increase, 5.9%; 98.3% CI: 3.2%, 9.1%), but use of concurrent CAD increased the per-polyp sensitivity for only those polyps 5 mm or smaller (mean increase, 4.8%; 98.3% CI: 2.2%, 7.9%).

Conclusion: Use of second-read CAD significantly improves readers' per-patient and per-polyp detection. Concurrent CAD is less effective.

Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100354/-/DC1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.10100354DOI Listing
February 2011

Polyp characteristics correctly annotated by computer-aided detection software but ignored by reporting radiologists during CT colonography.

Radiology 2009 Dec 29;253(3):715-23. Epub 2009 Sep 29.

Department of Specialist X-Ray, University College Hospital, 2F Podium, 235 Euston Rd, London NW1 2BU, England.

Purpose: To retrospectively describe the characteristics of polyps incorrectly dismissed by radiologists despite appropriate computer-aided detection (CAD) prompting during computed tomographic (CT) colonography.

Materials And Methods: Ethics committee approval and patient informed consent were obtained from institutions that provided the data sets used in this HIPAA-compliant study. A total of 111 polyps that had a diameter of at least 6 mm and were detected with CAD were collated from three previous studies in which researchers investigated radiologist performance with and without CAD (total, 25 readers). Two new observers graded each polyp with predefined criteria, including polyp size, morphology, and location; data set quality; ease of visualization; tagging use and polyp coating; colonic curvature; CAD mark obscuration; and number of false-positive findings. The 86 polyps that were missed before CAD (those that were unreported by one or more original readers) were divided into those that remained unreported after CAD (no CAD gain, n = 36) and those that were reported correctly by at least one additional reader (CAD gain, n = 50). Logistic-regression analysis and the Fisher exact and Mann-Whitney tests were used to compare the results of both groups with each other and with a control group of 25 polyps, all of which were detected by readers without CAD.

Results: Before CAD, polyps 10 mm in diameter or larger, those that were rated easy to visualize, and those that were uncoated by tagged fluid were less likely to be missed (72%, 76%, and 80% of control polyps vs 43%, 43%, and 59% of missed polyps, respectively; P < .001, P < .01, and P < .03, respectively). After CAD, the odds of CAD gain decreased with increasing polyp size (odds ratio, 0.92; 95% confidence interval: 0.85, 1.00; P = .04) and irregular morphology (odds ratio, 0.28; 95% confidence interval: 0.08, 0.92; P = .04).

Conclusion: Larger irregular polyps are a common source of incorrect radiologist dismissal, despite correct CAD prompting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2533090356DOI Listing
December 2009

CT colonography: automated measurement of colonic polyps compared with manual techniques--human in vitro study.

Radiology 2007 Jan 14;242(1):120-8. Epub 2006 Nov 14.

Department of Imaging, University College Hospital, 2F Podium, 235 Euston Rd, London NW1 2BU, England.

Purpose: To prospectively investigate the relative accuracy and reproducibility of manual and automated computer software measurements by using polyps of known size in a human colectomy specimen.

Materials And Methods: Institutional review board approval was obtained for the study; written consent for use of the surgical specimen was obtained. A colectomy specimen containing 27 polyps from a 16-year-old male patient with familial adenomatous polyposis was insufflated, submerged in a container with solution, and scanned at four-section multi-detector row computed tomography (CT). A histopathologist measured the maximum dimension of all polyps in the opened specimen. Digital photographs and line drawings were produced to aid CT-histologic measurement correlation. A novice (radiographic technician) and an experienced (radiologist) observer independently estimated polyp diameter with three methods: manual two-dimensional (2D) and manual three-dimensional (3D) measurement with software calipers and automated measurement with software (automatic). Data were analyzed with paired t tests and Bland-Altman limits of agreement.

Results: Seven polyps (
Conclusion: For polyps smaller than 1 cm, measurement differences of up to 2.5 mm are within the expected limits of inter- and intraobserver agreement for all measurement techniques. Automated and manual 3D polyp measurements are more accurate than manual 2D measurements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2421052068DOI Listing
January 2007

Computed tomographic colonography: assessment of radiologist performance with and without computer-aided detection.

Gastroenterology 2006 Dec 1;131(6):1690-9. Epub 2006 Oct 1.

Department of Specialist Radiology, University College Hospital, London, England.

Background & Aims: In isolation, computer-aided detection (CAD) for computed tomographic (CT) colonography is as effective as optical colonoscopy for detection of significant adenomas. However, the unavoidable interaction between CAD and the reader has not been addressed.

Methods: Ten readers trained in CT but without special expertise in colonography interpreted CT colonography images of 107 patients (60 with 142 polyps), first without CAD and then with CAD after temporal separation of 2 months. Per-patient and per-polyp detection were determined by comparing responses with known patient status.

Results: With CAD, 41 (68%; 95% confidence interval [CI], 55%-80%) of the 60 patients with polyps were identified more frequently by readers. Per-patient sensitivity increased significantly in 70% of readers, while specificity dropped significantly in only one. Polyp detection increased significantly with CAD; on average, 12 more polyps were detected by each reader (9.1%, 95% CI, 5.2%-12.8%). Small- (< or =5 mm) and medium-sized (6-9 mm) polyps were significantly more likely to be detected when prompted correctly by CAD. However, overall performance was relatively poor; even with CAD, on average readers detected only 10 polyps (51.0%) > or =10 mm and 24 (38.2%) > or =6 mm. Interpretation time was shortened significantly with CAD: by 1.9 minutes (95% CI, 1.4-2.4 minutes) for patients with polyps and by 2.9 minutes (95% CI, 2.5-3.3 minutes) for patients without. Overall, 9 readers (90%) benefited significantly from CAD, either by increased sensitivity and/or by reduced interpretation time.

Conclusions: CAD for CT colonography significantly increases per-patient and per-polyp detection and significantly reduces interpretation times but cannot substitute for adequate training.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2006.09.051DOI Listing
December 2006

Computer assisted detection software for CT colonography: effect of sphericity filter on performance characteristics for patients with and without fecal tagging.

Eur Radiol 2007 Mar 5;17(3):662-8. Epub 2006 Oct 5.

Medicsight PLC, Berkeley Sq, London, UK.

The aim of this study is to investigate the effect of changing sphericity filter values on performance of a computer assisted detection (CAD) system for CT colonography for data with and without fecal tagging. Colonography data from 138 patients with 317 validated polyps were divided into those with (86) and without (52) fecal tagging. Polyp coordinates were established by three observers and datasets analysed subsequently by a proprietary CAD system used at four discrete sphericity filter settings. Prompts were compared with the known coordinates in order to determine sensitivity and specificity. Sensitivity was highest at low sphericity; of 164 polyps 6 mm or more, 144 (87.8%) were detected at sphericity 0.3, and 132 (80.1%) at sphericity 0.9. Of 42 polyps measuring 10 mm or more, 40 (95.2%) were detected at sphericity 0.3, and 36 (85.7%) at sphericity 0.9. There was no significant difference in sensitivity for tagged and un-tagged data but specificity was reduced in tagged data at low sphericity and significantly reduced in untagged data at high sphericity. CAD had a sensitivity of 95.2% for polyps measuring 1 cm or more and 87.8% for polyps 6 mm or more when used at a sphericity setting of 0.3. Higher sphericity settings increased specificity while reducing sensitivity. The bowel preparation used significantly impacts on specificity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-006-0430-zDOI Listing
March 2007

Polyp measurement and size categorisation by CT colonography: effect of observer experience in a multi-centre setting.

Eur Radiol 2006 Aug 25;16(8):1737-44. Epub 2006 Apr 25.

Intestinal Imaging Centre, St. Marks Hospital, London, UK.

The extent measurement error on CT colonography influences polyp categorisation according to established management guidelines is studied using twenty-eight observers of varying experience to classify polyps seen at CT colonography as either 'medium' (maximal diameter 6-9 mm) or 'large' (maximal diameter 10 mm or larger). Comparison was then made with the reference diameter obtained in each patient via colonoscopy. The Bland-Altman method was used to assess agreement between observer measurements and colonoscopy, and differences in measurement and categorisation was assessed using Kruskal-Wallis and Chi-squared test statistics respectively. Observer measurements on average underestimated the diameter of polyps when compared to the reference value, by approximately 2-3 mm, irrespective of observer experience. Ninety-five percent limits of agreement were relatively wide for all observer groups, and had sufficient span to encompass different size categories for polyps. There were 167 polyp observations and 135 (81%) were correctly categorised. Of the 32 observations that were miscategorised, 5 (16%) were overestimations and 27 (84%) were underestimations (i.e. large polyps misclassified as medium). Caution should be exercised for polyps whose colonographic diameter is below but close to the 1-cm boundary threshold in order to avoid potential miscategorisation of advanced adenomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-006-0189-2DOI Listing
August 2006

CT colonography interpretation times: effect of reader experience, fatigue, and scan findings in a multi-centre setting.

Eur Radiol 2006 Aug 25;16(8):1745-9. Epub 2006 Apr 25.

Intestinal Imaging Centre, St. Marks Hospital, London, UK.

Our purpose was to assess the effect of reader experience, fatigue, and scan findings on interpretation time for CT colonography. Nine radiologists (experienced in CT colonography); nine radiologists and ten technicians (both groups trained using 50 validated examinations) read 40 cases (50% abnormal) under controlled conditions. Individual interpretation times for each case were recorded, and differences between groups determined. Multi-level linear regression was used to investigate effect of scan category (normal or abnormal) and observer fatigue on interpretation times. Experienced radiologists (mean time 10.9 min, SD 5.2) reported significantly faster than less experienced radiologists and technicians; odds ratios of reporting times 1.4 (CI 1.1, 1.8) and 1.6 (1.3, 2.0), respectively (P
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-006-0190-9DOI Listing
August 2006

Computer-assisted reader software versus expert reviewers for polyp detection on CT colonography.

AJR Am J Roentgenol 2006 Mar;186(3):696-702

Department of Intestinal Imaging, St. Mark's and Northwick Park Hospitals, Watford Rd., Harrow HA1 3UJ, United Kingdom.

Objective: The purpose of our study was to assess the sensitivity of computer-assisted reader (CAR) software for polyp detection compared with the performance of expert reviewers.

Materials And Methods: A library of colonoscopically validated CT colonography cases were collated and separated into training and test sets according to the time of accrual. Training data sets were annotated in consensus by three expert radiologists who were aware of the colonoscopy report. A subset of 45 training cases containing 100 polyps underwent batch analysis using ColonCAR version 1.2 software to determine the optimum polyp enhancement filter settings for polyp detection. Twenty-five consecutive positive test data sets were subsequently interpreted individually by each expert, who was unaware of the endoscopy report, and before generation of the annotated reference via an unblinded consensus interpretation. ColonCAR version 1.2 software was applied to the test cases, at optimized polyp enhancement filter settings, to determine diagnostic performance. False-positive findings were classified according to importance.

Results: The 25 test cases contained 32 nondiminutive polyps ranging from 6 to 35 mm in diameter. The ColonCAR version 1.2 software identified 26 (81%) of 32 polyps compared with an average sensitivity of 70% for the expert reviewers. Eleven (92%) of 12 polyps > or = 10 mm were detected by ColonCAR version 1.2. All polyps missed by experts 1 (n = 4) and 2 (n = 3) and 12 (86%) of 14 polyps missed by expert 3 were detected by ColonCAR version 1.2. The median number of false-positive highlights per case was 13, of which 91% were easily dismissed.

Conclusion: ColonCAR version 1.2 is sensitive for polyp detection, with a clinically acceptable false-positive rate. ColonCAR version 1.2 has a synergistic effect to the reviewer alone, and its standalone performance may exceed even that of experts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2214/AJR.04.1990DOI Listing
March 2006

Computed tomography colonography: automated diameter and volume measurement of colonic polyps compared with a manual technique--in vitro study.

J Comput Assist Tomogr 2005 May-Jun;29(3):387-93

Intestinal Imaging Centre, St. Mark's Hospital, Northwick Park, London, United Kingdom.

Objective: To investigate inter- and intraobserver agreement of automated measurement of polyp diameter in vitro.

Methods: Two phantoms ("QRM" and "Whiting") containing simulated polyps of known diameter and volume were scanned using 16-detector row computed tomography. Two observers estimated polyp diameter using 3 methods: software calipers ("manual"), freehand boundary identification ("semiautomatic"), and automated software segmentation ("fully automatic").

Results: Intraobserver 95% limits of agreement for diameter were narrowest for the fully automatic method (QRM span: 0.39 mm, 0.48 mm; Whiting span: 0.24 mm, 0 mm). Manual estimates were approximately 10 times wider (QRM span: 3.57 mm, 3.21 mm; Whiting span: 3.2 mm, 2.02 mm). Volume estimates were narrowest for the fully automatic method (span: 24.2 mm, 24.1 mm vs. 97.9 mm, 102.9 mm for semiautomatic measurement). Interobserver agreement for diameter was narrowest for the fully automatic method (QRM span: 0.12 mm, Whiting span: 0.16 mm), with the manual method approximately 18 times wider (QRM span: 2.87 mm, Whiting span: 2.18 mm).

Conclusion: Fully automated measurement of polyp diameter and volume is technically feasible and results in superior inter- and intraobserver agreement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.rct.0000160985.66259.96DOI Listing
June 2005
-->