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1.
Article in English | MEDLINE | ID: mdl-38590110

ABSTRACT

BACKGROUND AND AIMS: Assessment and scoring of histological images in Ulcerative colitis (UC) is prone to inter- and intra-observer variability. This study aimed to investigate whether an artificial intelligence (AI) system developed using image processing and machine learning algorithms could measure histological disease activity based on the Nancy index. METHODS: A total of 200 histological images of patients with UC were used in this study. A novel AI algorithm was developed using state-of-the-art image processing and machine learning algorithms based on deep learning and feature extraction. The cell regions of each image, followed by the Nancy index, were manually annotated and measured independently by four histopathologists. Manual and AI-automated measurements of the Nancy index score were conducted and assessed using the intraclass correlation coefficient (ICC). RESULTS: The 200-image dataset was divided into two groups (80% was used for training and 20% for testing). Intraclass correlation coefficient statistical analyses were performed to evaluate the AI tool and used as a reference to calculate the accuracy. The average ICC among the histopathologists was 89.3 and the average ICC between histopathologists and the AI tool was 87.2. The AI tool was found to be highly correlated with histopathologists. CONCLUSIONS: The high correlation of performance of the AI method suggests promising potential for inflammatory bowel disease clinical applications. A standardized automated histological AI-driven scoring system can potentially be used in daily inflammatory bowel disease practice to reduce training needs and resource use, eliminate the subjectivity of the pathologists, and assess disease severity for treatment decisions.

2.
Lancet Rheumatol ; 5(10): e611-e621, 2023 Oct.
Article in English | MEDLINE | ID: mdl-38251485

ABSTRACT

BACKGROUND: Vascular fibrosis is a key manifestation of systemic sclerosis that leads to the narrowing of small and medium arteries, causing vascular clinical manifestations including digital ulcers and pulmonary arterial hypertension. We investigated the potential of the MRI-based Digital Artery Volume Index (DAVIX) as a surrogate outcome measure of vascular fibrosis by using it to quantify and predict the burden of digital ulcer disease in patients with systemic sclerosis. METHODS: Two independent cohorts of patients participating in the prospective observational study STRIKE were consecutively enrolled from the Scleroderma Clinic of the Leeds Teaching Hospitals Trust, Leeds, UK. Eligible patients were aged 18 years or older and fulfilled the very early diagnosis of systemic sclerosis (VEDOSS) or the 2013 American College of Rheumatology (ACR)-European Alliance of Associations for Rheumatology (EULAR) systemic sclerosis classification criteria. DAVIX was calculated as the percentage mean of the ratio of digital artery volume to finger volume in the four fingers of the dominant hand. Data were collected at baseline and 12-month follow-up, and the primary outcome was the presence of digital ulcers at 12-month follow-up. FINDINGS: Between Feb 7, 2018, and April 11, 2022, we included 85 patients in the exploratory cohort and 150 in the validation cohort. In the exploratory cohort, the mean age was 54·5 years (SD 11·6), 75 (88%) of 85 patients were women, ten (12%) were men, and 69 (82%) were White. In the validation cohort, the mean age was 53·5 years (SD 13·8), 136 (91%) of 150 patients were women, 14 (9%) were men, and 127 (85%) were White. In the exploratory cohort, DAVIX was significantly lower in patients with previous or active digital ulcers (0·34% [IQR 0·16-0·69]) than in those without digital ulcer disease (0·65% [0·42-0·88]; p=0·015); this finding was substantiated in the validation cohort (0·43% [0·20-0·73] vs 0·73% [0·53-0·97]; p<0·0001). Patients who developed new digital ulcers during 12-month follow-up had a lower DAVIX (0·23% [0·10-0·66]) than those who did not (0·65% [0·45-0·91]; p=0·0039). DAVIX was negatively correlated with disease duration (r=-0·415; p<0·0001), the ratio of forced vital capacity to the diffusing capacity of the lungs for carbon monoxide (r=-0·334; p=0·0091), nailfold capillaroscopy pattern (r=-0·447; p<0·0001), and baseline modified Rodnan skin score (r=-0·305; p=0·014) and was positively correlated with the diffusing capacity of carbon monoxide (r=0·368; p=0·0041). DAVIX was negatively correlated with change in score on the Scleroderma Health Assessment Questionnaire-Disability Index (r=-0·308; p=0·024), Visual Analogue Scale (VAS) Raynaud's (r=-0·271; p=0·044), and VAS digital ulcers (r=-0·291; p=0·044). INTERPRETATION: DAVIX is a promising surrogate outcome measure of digital ulcer disease in patients with systemic sclerosis. The ability of DAVIX to non-invasively predict future digital ulcers and worsening of patient-reported outcomes could aid patient enrichment and stratification in clinical trials. Clinically, DAVIX could offer insights into the assessment of vascular activity. The sensitivity of DAVIX to change over time and with treatment will establish its value as an imaging outcome measure of vascular disease. FUNDING: National Institute for Health Research Biomedical Research Centre and University of Leeds Industry Engagement Accelerator Fund.


Subject(s)
Scleroderma, Localized , Scleroderma, Systemic , Skin Ulcer , Male , Humans , Female , Middle Aged , Carbon Monoxide , Prospective Studies , Scleroderma, Systemic/complications , Ulnar Artery , Magnetic Resonance Imaging , Outcome Assessment, Health Care , Fibrosis
3.
ACR Open Rheumatol ; 4(8): 721-734, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35689340

ABSTRACT

OBJECTIVE: To summarize the feasibility of computer-assisted quantification of joint pathologies on magnetic resonance imaging (MRI) in patients with inflammatory arthritis by evaluating the published data on reliability, validity, and feasibility. METHODS: A systematic literature search was performed for original articles published from January 1, 1985, to January 1, 2021. We selected studies in which patients with inflammatory arthritis were enrolled, and arthritis-related structural damage/synovitis in peripheral joints was assessed on non-contrast-enhanced, contrast-enhanced (CE), or dynamic CE (DCE)-MRI using (semi)automated methods. Data were pooled using random-effects model. RESULTS: Twenty-eight studies consisting of 1342 MRIs were included (mean age, 54.8 years; 66.7% female; duration of arthritis, 3.6 years). Among clinical/laboratory factors, synovial membrane volume (SV) was moderately correlated with erthrocyte sedimentation rate (ESR) level (P < 0.01). Pooled analysis showed an overall excellent intra- and inter-reader reliability for computer-aided quantification of bone erosion volume (BEV; r = 0.97 [95% CI: 0.92-0.99], 0.93 [0.87-0.97]), SV (r = 0.98 [95% CI: 0.90-0.99], 0.86 [0.78-0.91]), and DCE-MRI perfusion parameters (r = 0.96-0.99). Meta-regression showed that computer-aided and manual methods provide comparable reliability (P > 0.05). Computer-aided measurement of BEV (r = 0.92), SV (r = 0.82), and DCE-MRI biomarkers (r = 0.72 N-total; r = 0.74 N-plateau; r = 0.64 N-washout) were significantly correlated with the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS; P < 0.01), allowing for earlier assessment of drug efficacy. On average, (semi)automated analysis of BEV/SV took 17 minutes (vs. 9 minutes for the RAMRIS) and DCE-MRI took 4 minutes (vs. 33 minutes for manual assessment). CONCLUSION: Computer-aided image quantification technologies demonstrate excellent reliability and validity when used to quantify MRI pathologies of peripheral joints in patients with inflammatory arthritis. Computer-aided evaluation of inflammatory arthritis is an emerging field and should be considered as a viable complement to conventional observer-based scoring methods for clinical trials application.

4.
RMD Open ; 8(1)2022 03.
Article in English | MEDLINE | ID: mdl-35347068

ABSTRACT

OBJECTIVE: Can ultrasound (US), MRI and X-ray applied to the distal interphalangeal (DIP)-joint and synovio-entheseal complex (SEC) discriminate between patients with psoriatic arthritis (PsA), skin psoriasis (PsO) and hand osteoarthritis (OA)? METHODS: In this prospective, cross-sectional study, patients with DIP-joint PsA and nail involvement (n=50), PsO with nail involvement (n=12); and OA (n=13); were consecutively recruited. Risk ratios (RR) were calculated for US, MRI and X-ray findings of the DIP-joint and SEC between diagnoses. RESULTS: New bone formation (NBF) in US and MRI was a hallmark of OA, reducing the risk of having PsA (RR 0.52 (95% CI 0.43 to 0.63) and 0.64 (95% CI 0.56 to 0.74). The OA group was different from PsA and PsO on all MRI and X-ray outcomes reflected in a lower RR of having PsA; RR ranging from 0.20 (95% CI 0.13 to 0.31) for MRI bone marrow oedema (BMO) to 0.85 (95% CI 0.80 to 0.90) in X-ray enthesitis. No outcome in US, MRI or X-ray was significantly associated with a higher risk of PsA versus PsO, although there was a trend to a higher degree of US erosions and NBF in PsA. 82% of PsA and 67% of PsO was treated with disease modifying antirheumatic drugs which commonly reflects the clinical setting. CONCLUSION: High grade of US, MRI and X-ray NBF reduce the RR of having PsA compared with OA. In PsA versus PsO patients, there was a trend for US to demonstrate more structural changes in PsA although this did not reach significance.


Subject(s)
Arthritis, Psoriatic , Osteoarthritis , Psoriasis , Arthritis, Psoriatic/complications , Arthritis, Psoriatic/diagnostic imaging , Arthritis, Psoriatic/drug therapy , Cross-Sectional Studies , Humans , Multimodal Imaging , Osteoarthritis/complications , Osteoarthritis/diagnostic imaging , Prospective Studies , Psoriasis/diagnosis , Psoriasis/diagnostic imaging
5.
Orphanet J Rare Dis ; 16(1): 109, 2021 02 27.
Article in English | MEDLINE | ID: mdl-33639990

ABSTRACT

BACKGROUND: PIK3CA-related overgrowth spectrum (PROS) refers to a group of rare disorders, caused by somatic activating mutations in PIK3CA, resulting in abnormal PI3K-AKT-mTOR pathway signalling. Significant associated morbidity is frequently observed, and approved treatments are lacking. Miransertib (ARQ 092) is a novel, orally available, selective pan-AKT inhibitor with proven in vitro efficacy. Following recent results of the use of AKT inhibitors in Proteus syndrome (PS) and AKT-mutant cancers, we investigated its therapeutic use in two patients with severe PROS who had exhausted conventional treatment methods. RESULTS: Two patients, one with CLOVES variant (P1) and one with facial infiltrating lipomatosis and hemimegalencephaly (P2), were commenced on miransertib treatment on a compassionate use basis. In patient one, intra-abdominal and paraspinal overgrowth had resulted in respiratory compromise, obstructive uropathy, dysfunctional seating and lying postures, and chronic pain. In patient two, hemifacial overgrowth and hemimegalencephaly had caused difficulties with articulation and oral function, and refractory epilepsy. Miransertib treatment was continued for a median duration of 22 months (range 22-28). In patient one, alleviation of respiratory compromise was observed and functionally, seating and lying postures improved. Serial volumetric MRI analysis revealed 15% reduction in calculated volumes of fatty overgrowth between treatment commencement and end. In patient two, reduction in seizure burden and improved parent-reported quality of life measures were reported. Treatment was discontinued in both patients due to lack of sustained response, and poor compliance in year two of treatment (P2). No significant toxicities were reported. CONCLUSION: We report the first paediatric case series of the use of miransertib in two children with PROS. Objective clinical response was observed in patient one, and improvement in key qualitative outcomes was reported in patient two. Treatment was well tolerated with no significant toxicities reported. This case series highlights the potential therapeutic utility of miransertib in selected paediatric patients with severe PROS, and further demonstrates the potential for re-purposing targeted therapies for the treatment of rare diseases. An open label, Phase 1/2 study of miransertib in children with PROS and PS is underway to more accurately assess the efficacy of miransertib in the treatment of PROS disorder (NCT03094832).


Subject(s)
Phosphatidylinositol 3-Kinases , Quality of Life , Aminopyridines , Child , Class I Phosphatidylinositol 3-Kinases/genetics , Humans , Imidazoles , Mutation , Proto-Oncogene Proteins c-akt/genetics
6.
Knee ; 28: 256-265, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33453514

ABSTRACT

OBJECTIVE: This study investigated the effect of exercise therapy on inflammatory activity in synovitis and bone marrow lesions (BMLs) assessed by magnetic resonance imaging (MRI) in patients with knee OA. METHODS: 60 patients with knee OA were randomized 1:1 to 12 weeks of supervised exercise therapy 3 times/week (ET) or a no-attention control group (CG). Synovitis and BMLs were assessed with static MRI with and without contrast and with dynamic contrast enhanced MRI (DCE-MRI). DCE-MRI data was quantified using pixel-by-pixel methodology based on analysis of signal intensity curves. Pain was assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Analyses of covariance were used assessing group differences in changes from baseline to week 12. RESULTS: 33 patients adhered to the protocol and had valid MRI and KOOS data (ET, n = 16, CG, n = 17). Statistically significant and clinically relevant group difference in favour of ET was seen in KOOS pain change (-11.7 points, 95%CI: -20.1 to -3.4). There were statistically significant group differences in DCE-MRI assessed synovitis in the anterior synovium with unchanged inflammatory activity in the ET group compared to the CG. There were no group differences in BMLs and static MRI. CONCLUSION: Inflammatory activity was unchanged, and pain was reduced in patients with knee OA adhering to 12 weeks of exercise therapy compared to a no-attention control group. The reduction in pain was not explained by changes in inflammatory activity. Overall, the results suggest that exercise is not harmful in knee OA. ClinicalTrials.gov number: NCT01545258.


Subject(s)
Exercise Therapy , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/rehabilitation , Synovitis/diagnostic imaging , Aged , Female , Humans , Knee Joint/diagnostic imaging , Magnetic Resonance Imaging , Male , Middle Aged , Pain Measurement
7.
Curr Probl Diagn Radiol ; 50(3): 430-435, 2021.
Article in English | MEDLINE | ID: mdl-32703538

ABSTRACT

The clinical management of COVID-19 is challenging. Medical imaging plays a critical role in the early detection, clinical monitoring and outcomes assessment of this disease. Chest x-ray radiography and computed tomography) are the standard imaging modalities used for the structural assessment of the disease status, while functional imaging (namely, positron emission tomography) has had limited application. Artificial intelligence can enhance the predictive power and utilization of these imaging approaches and new approaches focusing on detection, stratification and prognostication are showing encouraging results. We review the current landscape of these imaging modalities and artificial intelligence approaches as applied in COVID-19 management.


Subject(s)
Artificial Intelligence , COVID-19/prevention & control , Diagnostic Imaging/methods , Image Interpretation, Computer-Assisted/methods , Humans , SARS-CoV-2
8.
Curr Probl Diagn Radiol ; 50(2): 262-267, 2021.
Article in English | MEDLINE | ID: mdl-32591104

ABSTRACT

Artificial intelligence (AI) is poised to make a veritable impact in medicine. Clinical decision support (CDS) is an important area where AI can augment the clinician's capability to collect, understand and make inferences on an overwhelming volume of patient data to reach the optimal clinical decision. Advancements in medical image analysis, such as Radiomics, and data computation, such as machine learning, have expanded our understanding of disease processes and their management. In this article, we review the most relevant concepts of AI as applicable to advanced imaging-based clinical decision support systems.


Subject(s)
Decision Support Systems, Clinical , Artificial Intelligence , Diagnostic Imaging , Humans , Machine Learning , Radiography
11.
BMC Rheumatol ; 4: 33, 2020.
Article in English | MEDLINE | ID: mdl-32514494

ABSTRACT

In this commentary, we discuss the potential of advanced imaging, particularly Dynamic Contrast Enhanced (DCE) magnetic resonance imaging (MRI) for the objective assessment of the inflammatory process in rheumatoid arthritis (RA). We emphasise the potential of DCE-MRI in advancing the field and exploring new areas of research and development in RA. We hypothesize that different grades of bone marrow edema (BME) and synovitis in RA can be examined and monitored in a more sensitive manner with DCE-MRI. Future treatments for RA may benefit from the application of enhanced imaging of BMEs and synovitis. DCE-MRI may also facilitate enhanced stratification and phenotyping of patients enrolled in clinical trials.

12.
Drug Discov Today ; 25(3): 582-592, 2020 03.
Article in English | MEDLINE | ID: mdl-31954664

ABSTRACT

Reporter gene imaging (RGI) is described as the methodology that involves imaging of the encoding proteins that can be used as surrogate markers when fused with regulatory regions of the gene of interest. It provides a means to indirectly monitor molecular processes that are implicated in the pathophysiology of several diseases. The modalities utilized in RGI include MRI, PET, SPECT, as well as optical imaging modalities, such as bioluminescence and fluorescence. RGI provides a highly specific way to qualitatively and quantitatively assess cell targeting, transfection, protein expression and other intracellular processes, which are valuable for pharmacodynamic and pharmacokinetic assessment of cellular, gene and oncolytic viral therapeutics.


Subject(s)
Drug Development/methods , Genes, Reporter/genetics , Proteins/genetics , Animals , Biomarkers/metabolism , Humans , Magnetic Resonance Imaging , Optical Imaging , Positron-Emission Tomography , Proteins/metabolism , Tomography, Emission-Computed, Single-Photon
14.
Front Nutr ; 6: 105, 2019.
Article in English | MEDLINE | ID: mdl-31355205

ABSTRACT

Skeletal muscle disuse leads to atrophy, declines in muscle function, and metabolic dysfunction that are often slow to recover. Strategies to mitigate these effects would be clinically relevant. In a double-blind randomized-controlled pilot trial, we examined the safety and tolerability as well as the atrophy mitigating effect of a novel amino acid composition (AXA2678), during single limb immobilization. Twenty healthy young men were randomly assigned (10 per group) to receive AXA2678 or an excipient- and energy-matched non-amino acid containing placebo (PL) for 28d: days 1-7, pre-immobilization; days 8-15, immobilization; and days 16-28 post-immobilization recovery. Muscle biopsies were taken on d1, d8 (immobilization start), d15 (immobilization end), and d28 (post-immobilization recovery). Magnetic resonance imaging (MRI) was utilized to assess quadriceps muscle volume (Mvol), muscle cross-sectional area (CSA), and muscle fat-fraction (FF: the fraction of muscle occupied by fat). Maximal voluntary leg isometric torque was assessed by dynamometry. Administration of AXA2678 attenuated muscle disuse atrophy compared to PL (p < 0.05) with changes from d8 to d15 in PL: ΔMvol = -2.4 ± 2.3% and ΔCSA = -3.1% ± 2.1%, both p < 0.001 vs. zero; against AXA2678: ΔMvol: -0.7 ± 1.8% and ΔCSA: -0.7 ± 2.1%, both p > 0.3 vs. zero; and p < 0.05 between treatment conditions for CSA. During immobilization, muscle FF increased in PL but not in AXA2678 (PL: 12.8 ± 6.1%, AXA2678: 0.4 ± 3.1%; p < 0.05). Immobilization resulted in similar reductions in peak leg isometric torque and change in time-to-peak (TTP) torque in both groups. Recovery (d15-d28) of peak torque and TTP torque was also not different between groups, but showed a trend for better recovery in the AXA2678 group. Thrice daily consumption of AXA2678 for 28d was found to be safe and well-tolerated. Additionally, AXA2678 attenuated atrophy, and attenuated accumulation of fat during short-term disuse. Further investigations on the administration of AXA2678 in conditions of muscle disuse are warranted. Clinical Trial Registration: https://clinicaltrials.gov, identifier: NCT03267745.

15.
Biochem Pharmacol ; 165: 41-48, 2019 07.
Article in English | MEDLINE | ID: mdl-30831073

ABSTRACT

The success of disease-modifying osteoarthritis drug (DMOAD) development is still elusive. While there have been successes in preclinical and early clinical studies, phase 3 clinical trials have failed so far and there is still no approved, widely available DMOAD on the market. The latest research suggests that, among other causes, poor trial outcomes might be explained by the fact that osteoarthritis (OA) is a heterogeneous disease with distinct phenotypes. OA trials might be more successful if they would address and target a specific phenotype. The increasing availability of advanced techniques to detect particular OA characteristics expands the possibilities to distinguish between such potential OA phenotypes. Magnetic resonance imaging is among the key imaging techniques to stratify and monitor patients with changes in bone, cartilage and inflammation. Biochemical markers have mainly used as secondary parameters and could further delineate phenotypes. Moreover, post-hoc analyses of trial data have suggested the existence of distinct pain phenotypes and their relevance in the design of clinical trials. Although ongoing work in the field supports the concept of OA heterogeneity, this has not yet resulted in more effective treatment options. This paper reviews the current knowledge about potential OA phenotypes and suggests that combining patient clinical data, quantitative imaging, biochemical markers and utilizing data-driven approaches in patient selection and efficacy assessment will allow for more successful development of effective DMOADs.


Subject(s)
Antirheumatic Agents/administration & dosage , Drug Delivery Systems/methods , Osteoarthritis/diagnostic imaging , Osteoarthritis/drug therapy , Phenotype , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Biomarkers/metabolism , Diphosphonates/administration & dosage , Humans , Osteoarthritis/metabolism
16.
PET Clin ; 13(4): 523-550, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30219186

ABSTRACT

Contrast-enhanced MR imaging (CE-MR imaging) is recommended for diagnosis and monitoring of infectious and most inflammatory joint diseases. CE-MR imaging clearly differentiates soft and bony tissue from fluid collections and infectious debris. To improve imaging information, a dynamic CE-MR imaging sequence (DCE-MR imaging) sequence can be applied using fast T1-weighted sequential image acquisition during contrast injection. Use of DCE-MR imaging allows robust extraction of quantitative information regarding blood flow and capillary permeability, especially when dedicated analysis methods and software are used to analyze contrast kinetics. This article describes principles of DCE-MR imaging for the assessment of infectious and inflammatory joint diseases.


Subject(s)
Contrast Media , Infections/diagnosis , Joint Diseases/diagnosis , Magnetic Resonance Imaging/methods , Arthritis/diagnosis , Humans , Osteitis/diagnosis , Synovitis/diagnosis
17.
Clin Exp Rheumatol ; 32(5): 647-52, 2014.
Article in English | MEDLINE | ID: mdl-25068921

ABSTRACT

OBJECTIVES: The aim of this study is to assess prospectively the effect of rituximab (RTX) on MRI features of wrist joint disease in patients affected by rheumatoid arthritis (RA). METHODS: Ten patients (6F/4M, mean age 52.9±15.5 years) diagnosed with IgM rheumatoid factor, anti-CCP positive, RA according to the 1987 ACR criteria were treated with a single course of RTX (2 infusions of 1000 mg, 15 days apart). MRI of the dominant hand was performed with a 0.2T extremity-dedicated machine using pre and post contrast T1 weighted SE, turbo 3D, and STIR sequences at baseline, and after 4 and 24 weeks. MRI was analysed using the OMERACT-RAMRIS score and the dynamic contrast-enhanced (DCE-MRI) technique for wrist synovitis, which calculates the enhancement ratio as both rate of early enhancement (REE) and relative enhancement (RE). The corresponding ME and IRE parameters were calculated also through a computer-aided semi-automated method on the mean of three MRI slices and on a small ROI positioned in the area of maximum enhancement. RESULTS: DAS significantly decreased during the study period (ANOVA for repeated measures, p=0.005). The RAMRIS score did not change along the study, whereas the dynamic MRI values RE, IRE and ME on the small ROI significantly decreased. RE, but not the RAMRIS synovitis score, significantly correlated with DAS at baseline, 1 and 6 months (p=0.005, 0.04, and 0.0007, respectively). CONCLUSIONS: RTX confirmed good clinical efficacy, which was paralleled by a significant decrease in dynamic MRI results for wrist synovitis. On the contrary, the traditional RAMRIS measures did not change.


Subject(s)
Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Contrast Media , Magnetic Resonance Imaging , Synovial Membrane/drug effects , Synovitis/drug therapy , Wrist Joint/drug effects , Adult , Aged , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnosis , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Rituximab , Severity of Illness Index , Synovial Membrane/pathology , Synovitis/diagnosis , Time Factors , Treatment Outcome , Wrist Joint/pathology
18.
Rheumatology (Oxford) ; 53(4): 746-56, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24369412

ABSTRACT

OBJECTIVE: In a comparative conventional MRI, dynamic contrast-enhanced (DCE)-MRI, CT and radiography study, the authors aimed to monitor whether inflammation is reduced or even eliminated and damage halted in PsA patients receiving anti-TNF therapy. METHODS: A 48-week prospective open-label investigator-initiated trial of 41 biologic-naive patients treated with 40 mg adalimumab every other week. Hand CT, MRI (according to the PsA MRI scoring system method) and radiography (Sharp-van der Heijde method) were obtained at weeks 0, 6 (only MRI), 24 and 48. Clinical response was assessed by the PsA Response Criteria (PsARC). RESULTS: In the 23 PsARC responders at week 48, significant decreases from baseline in MRI synovitis (mean -2.0, P < 0.05), bone marrow oedema (BMO) (-1.3, P < 0.05), flexor tenosynovitis (-2.1, P < 0.05) and total inflammation (-6.0, P < 0.005) were observed. However, MRI signs of inflammation remained present (week 48 total inflammation score median = 9). Several DCE-MRI parameters also decreased (P < 0.05) and were correlated (ρ = 0.62) with conventional MRI total inflammation score. No statistically significant changes in bone erosion or proliferation scores were observed. With CT as the standard reference for detecting bone erosions/proliferations, sensitivity, specificity and accuracy were 100%/40%, 83%/93% and 84%/86%, respectively, for MRI, whereas corresponding values for radiography were 17%/26%, 98%/96%, and 93%/87%, respectively. Erosive progression as assessed by CT was found in 6 of 480 joints and baseline BMO was predictive (relative risk 10, 95% CI 2.1, 49). CONCLUSION: MRI signs of inflammation decrease, but do not disappear, during anti-TNF-α therapy. No overall changes in bone erosions or proliferations were observed. On joint-level baseline MRI, BMO was related to subsequent erosive progression detected by CT. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov/, NCT01465438.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Arthritis, Psoriatic/drug therapy , Hand Joints/diagnostic imaging , Adalimumab , Adult , Arthritis, Psoriatic/diagnostic imaging , Arthritis, Psoriatic/pathology , Disease-Free Survival , Female , Hand Joints/pathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Prospective Studies , Synovitis/diagnostic imaging , Synovitis/drug therapy , Synovitis/pathology , Tomography, X-Ray Computed , Treatment Outcome
19.
Eur J Radiol ; 82(8): 1286-91, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23562303

ABSTRACT

RATIONAL AND OBJECTIVE: Dynamic contrast enhanced (DCE)-MRI has great potential to provide quantitative measure of inflammatory activity in rheumatoid arthritis. There is no current benchmark to establish the stability of signal in the joints of healthy subjects when imaged with DCE-MRI longitudinally, which is crucial so as to differentiate changes induced by treatment from the inherent variability of perfusion measures. The objective of this study was to test a pixel-by-pixel parametric map based approach for analysis of DCE-MRI (Dynamika) and to investigate the variability in signal characteristics over time in healthy controls using longitudinally acquired images. MATERIALS AND METHODS: 10 healthy volunteers enrolled, dominant wrists were imaged with contrast enhanced 3T MRI at baseline, week 12, 24 and 52 and scored with RAMRIS, DCE-MRI was analysed using a novel quantification parametric map based approach. Radiographs were obtained at baseline and week 52 and scored using modified Sharp van der Heidje method. RAMRIS scores and dynamic MRI measures were correlated. RESULTS: No erosions were seen on radiographs, whereas MRI showed erosion-like changes, low grade bone marrow oedema and low-moderate synovial enhancement. The DCE-MRI parameters were stable (baseline scores, variability) (mean±st.dev); in whole wrist analysis, MEmean (1.3±0.07, -0.08±0.1 at week 24) and IREmean (0.008±0.004, -0.002±0.005 at week 12 and 24). In the rough wrist ROI, MEmean (1.2±0.07, 0.04±0.02 at week 52) and IREmean (0.001±0.0008, 0.0006±0.0009 at week 52) and precise wrist ROI, MEmean (1.2±0.09, 0.04±0.04 at week 52) and IREmean (0.001±0.0008, 0.0008±0.001 at week 24 and 52). The Dynamic parameters obtained using fully automated analysis demonstrated strong, statistically significant correlations with RAMRIS synovitis scores. CONCLUSION: The study demonstrated that contrast enhancement does occur in healthy volunteers but the inherent variability of perfusion measures obtained with quantitative DCE-MRI method is low and stable, suggesting its suitability for longitudinal studies of inflammatory arthritis. These results also provide important information regarding potential cut-off levels for imaging remission goals in patients with RA using both RAMRIS and DCE-MRI extracted parametric parameters.


Subject(s)
Algorithms , Gadolinium DTPA , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Pattern Recognition, Automated/methods , Wrist Joint/anatomy & histology , Adult , Contrast Media , Female , Healthy Volunteers , Humans , Image Enhancement/methods , Longitudinal Studies , Male , Reproducibility of Results , Sensitivity and Specificity , Young Adult
20.
J Rheumatol Suppl ; 89: 44-8, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22751591

ABSTRACT

OBJECTIVE: Dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI), the quantification of enhancement within the synovial membrane and bone by extracting curves using fast T1-weighted sequences during intravenous administration of contrast agent, evaluates synovitis and bone marrow edema in psoriatic arthritis (PsA). In this pilot study, we looked at possible differences between joint synovitis and tenosynovitis in PsA as compared with rheumatoid arthritis (RA). METHODS: Seven patients with PsA and 10 with RA were studied. After DCE-MRI was performed on 3 axial slices of the wrist, the enhancement ratio was calculated on 6 different regions of interest (ROI) of the synovial membrane outlined by the operator: the wrist compartment, 3 extensor tendon compartments, and 2 flexor compartments. DCE-MRI results were quantitatively analyzed using the Dynamika software, a computer-aided semiautomated method. RESULTS: In PsA, the area of the ROI outlined around the first and second extensor compartments was larger than in RA; the opposite was true for the extensor carpi ulnaris region. The volume of inflammation was significantly higher in RA than in PsA for all the extensor compartments except the second, and in the joint synovial membrane. The DCE-MRI indicators of the degree of inflammation were higher for PsA in the joint synovial membrane (p = 0.002 and p < 0.001, respectively). There was a significant correlation between volume of inflammation but not its degree and 28-joint Disease Activity Score at the level of the wrist joint (r = 0.6; p = 0.01). CONCLUSION: DCE-MRI can reveal useful and potentially clinically important information on the characteristics of different types of arthritis.


Subject(s)
Arthritis, Psoriatic/diagnosis , Contrast Media , Gadolinium DTPA , Hand Joints/pathology , Magnetic Resonance Imaging , Synovial Membrane/pathology , Synovitis/diagnosis , Tendons/pathology , Tenosynovitis/diagnosis , Aged , Arthritis, Psoriatic/pathology , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/pathology , Diagnosis, Differential , Female , Humans , Image Interpretation, Computer-Assisted , Italy , Male , Middle Aged , Pilot Projects , Predictive Value of Tests , Severity of Illness Index , Synovitis/pathology , Tenosynovitis/pathology
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