Registration of dynamic MRI data and its impact on diagnostic process

This paper discusses impact of a novel registration algorithm for dynamic MRI data on diagnosis of rheumatoid arthritis. The algorithm is based on a hybrid Euclidean-Lagrangian approach. It was applied to data acquired with low and higheld MRI scanners. The scans were processed with region-of-interest based and voxel-by-voxel approaches before and after the egistration. In this paper, we demonstrate that diagnostic parameters extracted from the data before and after the registration vary dramatically, which has a crucial effect on diagnostic decision. Application of the the proposed algorithm signicantly reduces artefacts incurred due to patient motion, which permits reduction of variability of the enhancement curves, yielding more distinguishable uptake, equilibrium and wash-out phases and more precise quantitative data analysis

Computer-Assisted Image Analysis in Assessment of Peripheral Joint MRI in Inflammatory Arthritis: A Systematic Review and Meta-analysis

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 0.05). 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

Dynamic Contrast Enhanced MRI Can Monitor the Very Early Inflammatory Treatment Response upon Intra-Articular Steroid Injection in the Knee Joint: A Case Report with Review of the Literature

Dynamic contrast-enhanced MRI in inflammatory arthritis, especially in conjunction with computer-aided analysis using appropriate dedicated software, seems to be a highly sensitive tool for monitoring the early inflammatory treatment response in patients with rheumatoid arthritis. This paper gives a review of the current knowledge of the emerging technique. The potential of the technique is demonstrated and discussed in the context of a case report following the early effect of an intra-articular steroid injection in a patient with rheumatoid arthritis flare in the knee

Clinical experience with the AKT1 inhibitor miransertib in two children with PIK3CA-related overgrowth syndrome.

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)

MRI Digital Artery Volume Index (DAVIX) as a surrogate outcome measure of digital ulcer disease in patients with systemic sclerosis: a prospective cohort study

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