Serial Magnetic Resonance Imaging Research Articles

P696 Initiation of Vedolizumab did not provoke new-onset spondylarthritis in patients with inflammatory bowel disease: A Prospective Study Including Rheumatological and Blinded Imaging Assessments

Abstract Background Prior case series indicated a temporal relationship between use of vedolizumab and new-onset spondyloarthritis. Methods We aimed to evaluate the relationship between initiation of vedolizumab and development of new-onset spondyloarthritis in patients with inflammatory bowel disease, through serial clinical evaluation and magnetic resonance imaging. A single-centre prospective observational study of 24 patients with inflammatory bowel disease. Patients were eligible if they had active ulcerative colitis or Crohn’s disease and initiating vedolizumab, had no prior history of arthritis or spondyloarthritis and suitable for undergoing serial magnetic resonance imaging. Clinical evaluation was performed by a rheumatologist prior to first dose of vedolizumab and at weeks 8 and 24 weeks after administration. Axial magnetic resonance imaging was performed at baseline, weeks 8 and 24 and evaluated by a blinded central reader. Results Nine tumour necrosis factor inhibitor-naïve patients (4 male; mean age 53.2 yrs; 6 ulcerative colitis; 3 Crohn’s disease) and eight tumour necrosis factor inhibitor-experienced patients (7 male; mean age 48 yrs; 3 ulcerative colitis; 5 Crohn’s disease) completed all assessments. No patients developed new features of axial arthritis either on clinical or blinded radiological assessment at weeks 8 or 24, nor any features of peripheral spondyloarthritis including inflammatory oligoarthritis, enthesitis, dactylitis, or psoriasis (nail, body, or scalp). Both the tumour necrosis factor inhibitor-naive and tumour necrosis factor inhibitor-experienced patients demonstrated good intestinal response to vedolizumab. Conclusion Initiation of vedolizumab did not induce new features of axial or peripheral spondyloarthritis in tumour necrosis factor inhibitor-experienced or tumour necrosis factor inhibitor-naive patients with inflammatory bowel disease.

P547 Improved clinical and radiologic healing of Crohn’s perianal fistulas using a novel coordinated care model optimising medical and surgical treatments: A prospective real-world observational study

Abstract Background Despite best standard care, sustained healing rates of Crohn’s perianal fistulas remain low. A novel coordinated multi-disciplinary care model optimising medical and surgical treatment was established with the aim to improve fistula healing rates. Methods A prospective real-world observational study evaluated the efficacy of this new care model in adults with Crohn’s perianal fistulas. Patients seen through the new care model were sequentially invited to participate, between March 2021 to April 2022, and included irrespective of disease activity, duration, or prior treatments. Three dynamic stages of care were directed towards patients’ clinical disease activity: stage A, active disease, focused on medical and surgical treatment optimisation; stage B, optimised treatments with a seton in situ, focused on definitive surgical management; and stage C, healed disease, focused on treatment maintenance. Endpoints included: [1] clinical fistula healing after a minimum of 12 months follow-up; [2] changes in radiologic disease activity and fibrosis on serial magnetic resonance imaging; and [3] proportion of patients requiring treatment optimisation. Results Sixty patients were included. At baseline, 47% were in stage A, 5% stage B, and 48% stage C. Median age was 40 years (IQR: 32-49), 52% were male, median perianal disease duration was 9 years (IQR: 2-16), and median attendance through the preexisting service was 6 years (IQR: 3-9). After a median of 22 months follow-up (IQR: 16-25), 83% had clinical healing which was significantly higher than baseline rates at study inclusion (83 vs 48%, p<0.001). For patients in stage A at baseline, 68% achieved clinical healing with estimated clinical healing rates of 39% (95%CI: 24-60) and 85% (95%CI: 64-97) at 1 and 2 years, respectively. This paralleled a significant reduction in radiologic disease activity and increase in radiologic fibrosis, with radiologic remission observed in 51% and radiologic response in 47% overall (Table 1). Patients who achieved clinical healing had significantly less radiologic disease activity and greater fibrosis compared to patients with non-healing fistulas. Overall, 53% had biologic dose escalation and 10% switched to an alternative biologic agent with the new care model. Thirty-seven percent underwent a median of two perianal surgical interventions (IQR: 1-3), 15% had closure or ablative techniques performed, and 15% had seton removal only. Conclusion A novel coordinated multi-disciplinary care model optimising medical and surgical treatments resulted in high rates of clinical healing and improved radiologic disease activity and fibrosis of Crohn’s perianal fistulas. Controlled-matched studies evaluating treatment optimisation are needed.

Radiation-Induced Cerebral Contrast Enhancements Strongly Share Ischemic Stroke Risk Factors

Background and purposeRadiation-induced cerebral contrast enhancements (RICE) are frequent following both photon and particularly proton radiotherapy and are associated with a significant risk for neurologic morbidity. Nevertheless, risk factors are poorly understood. A more robust understanding of RICE risk factors is crucial to improve management and offer adaptive therapy at the outset and during follow-up. Materials and methodsWe analyzed the comorbidities in detail of 190 consecutive adult patients treated at a single European national comprehensive cancer center with proton radiotherapy (PRT; 54Gy RBE) for LGG from 2010 to 2020 who were followed with serial clinical exams and magnetic resonance imaging for in median 5.6 years. ResultsClassical vascular risk factors including age (≥50 years vs. <50 years: 1.6-fold; p=0.0024), hypertension (2.7-fold; p=0.00012) and diabetes (11.7-fold; p=0.0066) were observed more frequently in the cohort who developed RICE. Dyslipidemia (2.1-fold), overweight (2.0-fold) and smoking (2.6-fold) as well as history of previous stroke (1.7-fold) were also more frequently observed in the RICE cohort, though these factors did not reach threshold for significance. Multivariable regression modelling supported the influence of age (p=0.05), arterial hypertension (p=0.01) and potentially male sex (p=0.02), diabetes (p=0.0008) and smoking (p=0.001) on RICE occurrence over time, independent of each other and further vascular risk factors. If RICE occurred, bevacizumab treatment was two-fold more frequently needed in the cohort with vascular risk factors, but RICE long-term prognosis did not differ between the RICE subcohort with and without vascular risk factors. ConclusionsThis is the first report in the literature demonstrating RICE strongly share vascular risk factors with ischemic stroke, which further enhances the nebulous understanding of the multifactorial pathophysiology of RICE. Classical vascular risk factors, especially age, hypertension and diabetes clearly correlated independently with RICE risk. Risk-adapted screening and management for RICE can be directly derived from this data to assist in clinical management.

Serial cardiac magnetic resonance imaging for guidance of therapy management in patients treated with anakinra due to recurrent pericarditis.

To determine the utility of serial cardiac magnetic resonance (CMR) imaging for guidance of therapy management in patients treated with anakinra due to recurrent pericarditis (RP), compared with C-reactive protein (CRP) assay alone. In 2018-21, we enrolled 18 (14.5 ± 1.8 years old, 72% males) consecutive RP patients treated with anakinra (100 mg/day in patients ≥ 18 years old; 2 mg/kg/day < 18 years old) due to RP corticosteroid-dependent or not responsive to colchicine or non-steroidal anti-inflammatory drugs. After hospitalization, they were 1:1 randomized to CMR [no pericardial oedema and/or late gadolinium enchantment (LGE)] or CRP (<0.6 mg/dL). Tests were repeated every 3 months until negative to halve the anakinra dosage and cessation. The idiopathic aetiology was the most prevalent (n = 8, 44%), followed by post-pericardiotomy (n = 6, 33%). After a median treatment period of 8.7 ± 3.6 months, CRP-guided RP patients experienced more recurrences than CMR-guided ones (6 vs. 1, P = 0.016), with the worst prognosis in terms of recurrences (log-rank, P = 0.025) and significantly increased time of treatment (12.7 ± 2 vs. 16.1 ± 3.4 months, P = 0.019). In a multivariable exploratory Cox regression model, the number of previous recurrences and the idiopathic aetiology were independent predictors of RP during the anakinra treatment. New recurrences were subsequently directed to CMR imaging, and therapy was modified according to the LGE/oedema trend. After 1-year follow-up, no further recurrence was detected. Among patients with RP and treated with anakinra, serial CMR imaging of the pericardium can be utilized as an imaging biomarker, more informative for therapy duration than the solely CRP assessment. NCT06071156.

Exuberant circumferential fibroproliferative neuromas in lipomatosis of nerve: a unifying theory. Illustrative case.

Lipomatosis of nerve (LN) is a rare disorder characterized by the massive enlargement of peripheral nerves, frequently accompanied by generalized fibroadipose proliferation and skeletal overgrowth. The authors have been routinely following a 20-year-old male for lipomatosis of median nerve at the wrist noted shortly after birth. He had undergone resection of the lesion accompanied by sural nerve grafting at another institution. Clinically, although his neurological loss of function has been stable, he has had continued soft tissue growth. Serial magnetic resonance imaging has revealed persistent LN proximal to the repair sites with evidence of fatty proliferation in the sural grafts and continued LN and fatty proliferation distally. There has been a progressive circumferential pattern of fibrosis around the proximal and distal suture lines, which has a similar radiological pattern to desmoid type fibromatosis (a pattern recently described in neuromuscular choristoma [NMC] desmoid-type fibromatosis). Considering the similar reaction of nerve in both LN and NMC despite differing genetic cascades, the authors believe a unifying process occurs in both lesions. The pattern of circumferential fibroproliferation would be most consistent with neuron-mediated growth from unspecified trophic factors, supporting a previously reported a nerve-derived "inside-out mechanism." The clinical consequences of this unifying process are presented.

Analysis of Hybrid Feature Optimization Techniques Based on the Classification Accuracy of Brain Tumor Regions Using Machine Learning and Further Evaluation Based on the Institute Test Data.

The goal of this study was to get optimal brain tumor features from magnetic resonance imaging (MRI) images and classify them based on the three groups of the tumor region: Peritumoral edema, enhancing-core, and necrotic tumor core, using machine learning classification models. This study's dataset was obtained from the multimodal brain tumor segmentation challenge. A total of 599 brain MRI studies were employed, all in neuroimaging informatics technology initiative format. The dataset was divided into training, validation, and testing subsets online test dataset (OTD). The dataset includes four types of MRI series, which were combined together and processed for intensity normalization using contrast limited adaptive histogram equalization methodology. To extract radiomics features, a python-based library called pyRadiomics was employed. Particle-swarm optimization (PSO) with varying inertia weights was used for feature optimization. Inertia weight with a linearly decreasing strategy (W1), inertia weight with a nonlinear coefficient decreasing strategy (W2), and inertia weight with a logarithmic strategy (W3) were different strategies used to vary the inertia weight for feature optimization in PSO. These selected features were further optimized using the principal component analysis (PCA) method to further reducing the dimensionality and removing the noise and improve the performance and efficiency of subsequent algorithms. Support vector machine (SVM), light gradient boosting (LGB), and extreme gradient boosting (XGB) machine learning classification algorithms were utilized for the classification of images into different tumor regions using optimized features. The proposed method was also tested on institute test data (ITD) for a total of 30 patient images. For OTD test dataset, the classification accuracy of SVM was 0.989, for the LGB model (LGBM) was 0.992, and for the XGB model (XGBM) was 0.994, using the varying inertia weight-PSO optimization method and the classification accuracy of SVM was 0.996 for the LGBM was 0.998, and for the XGBM was 0.994, using PSO and PCA-a hybrid optimization technique. For ITD test dataset, the classification accuracy of SVM was 0.994 for the LGBM was 0.993, and for the XGBM was 0.997, using the hybrid optimization technique. The results suggest that the proposed method can be used to classify a brain tumor as used in this study to classify the tumor region into three groups: Peritumoral edema, enhancing-core, and necrotic tumor core. This was done by extracting the different features of the tumor, such as its shape, grey level, gray-level co-occurrence matrix, etc., and then choosing the best features using hybrid optimal feature selection techniques. This was done without much human expertise and in much less time than it would take a person.

Impact of pulmonary valve replacement on ventricular function and cardiac events in patients with tetralogy of Fallot. A retrospective cohort study

Introduction and objectivesOur aim was to assess the impact of prosthetic pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot (rTOF) on changes in biventricular volumes and function and on adverse cardiac events. MethodsAdults with rTOF were identified from the SACHER-registry. Data from serial cardiac magnetic resonance imaging, echocardiography, exercise capacity and n-terminal pro b-type natriuretic peptide (NT-proBNP) were collected. The primary endpoint was right ventricular ejection fraction (RVEF) as measured by cardiac magnetic resonance. Secondary endpoints were biventricular volumes, left ventricular ejection fraction, exercise capacity and NT-proBNP levels, and time to adverse cardiac outcomes (atrial and ventricular arrhythmia, endocarditis). Associations between previous PVR and longitudinal changes in functional outcomes and time to adverse cardiac outcomes were analyzed using linear mixed-effects models and Cox proportional hazards models, respectively. ResultsA total of 308 patients (153 with and 155 without PVR) with 887 study visits were analyzed. Previous PVR was not significantly associated with changes in RVEF (CE, −1.33; 95%CI, −5.87 to 3.21; P=.566). Previous PVR was associated with lower right ventricular end-diastolic volume but had no significant effect on left ventricular ejection fraction, exercise capacity, or NT-proBNP-levels. Previous PVR was associated with an increased hazard of atrial arrhythmias (HR, 2.09; 95%CI, 1.17-3.72; P=.012) and infective endocarditis (HR, 12.72; 95%CI, 4.69-34.49; P<.0001) but not with an increased hazard of sustained ventricular arrhythmias (HR, 0.64; 95%CI, 0.18-2.27; P=.490). ConclusionsPrevious PVR was not significantly associated with changes in RVEF but was associated with an increased risk of atrial arrhythmias and infective endocarditis.

Initial experiences with amyloid‐related imaging abnormalities in patients receiving aducanumab following accelerated approval

AbstractBackgroundAducanumab is the first approved amyloid‐lowering immunotherapy for Alzheimer’s disease (AD). There is little real‐world data to guide the management of amyloid‐related imaging abnormality (ARIA), a potentially serious side‐effect requiring surveillance with serial magnetic resonance imaging (MRI). The current study seeks to characterize the symptoms, clinical course and management of ARIA in memory clinic patients treated with aducanumab.MethodWe conducted a non‐blinded, observational case series of patients who received aducanumab from June 16, 2021 to August 1, 2022 at the Butler Hospital Memory and Aging Program. Inclusion: (1) Clinical diagnosis of mild cognitive impairment (MCI) or mild dementia due to AD, (2) confirmed amyloid positivity (PET/CSF), and (3) Mini Mental State Exam (MMSE) = 20‐30. Exclusions: (1) MRI with &gt; 4 microhemorrhages, &gt; 1 area of superficial siderosis or significant cerebrovascular disease, (2) MRI contraindication, (3) anticoagulation and (4) unstable medical/psychiatric conditions. Participants received monthly aducanumab infusions, titrated to a dose of 10 mg/kg, with ApoE genotyping and enhanced MRI monitoring adapted from the phase 3 trials. The primary outcome of the study was the identification of ARIA‐E by MRI. Secondary outcomes included severity of ARIA, clinical course, and time to resolution.ResultOut of 24 patients treated with aducanumab, we identified ARIA‐E in 6 patients (25%), all ApoE‐ε4 carriers, and 4 of whom had moderate‐severe radiographic severity. Comorbid ARIA‐H occurred in 3 patients, 1 of whom also had new onset of cerebellar metastatic cancer. Symptomatic ARIA occurred in 3 patients and included headache, confusion, gait instability, and word‐finding difficulties. Treatment was discontinued in 4 cases of moderate‐severe ARIA‐E, temporarily held in 1 moderate/asymptomatic case, and dosed through in 1 mild/asymptomatic case. All cases of ARIA‐E resolved without hospitalization or corticosteroids (mean duration = 3 months, range, 1 ‐ 6 months).ConclusionAdditional amyloid‐lowering antibodies, associated with ARIA, may soon become clinically available. These data support the careful patient selection, ApoE genotyping, MRI surveillance and individualized dosing recommended in the updated FDA prescribing information and Appropriate Use Recommendations.

Cognitive status modifies the association between elevated cerebrospinal fluid phosphorylated tau and longitudinal cerebral blood flow changes over a 7‐year follow‐up period

AbstractBackgroundAlzheimer’s disease (AD) is associated with widespread reductions in cerebral blood flow (CBF), but the precise link between AD pathology and CBF is unclear. Hypoperfusion is a late‐stage event associated with tau, but not amyloid, pathology. We assessed whether baseline levels of cerebrospinal fluid (CSF)‐measured core AD pathology [β‐amyloid42 (Aβ42), phosphorylated tau (p‐tau)] related to CBF changes over a 7‐year period and if associations differed by baseline cognitive status.MethodsVanderbilt Memory and Aging Project participants free of clinical dementia or stroke at enrollment [n = 153, 72±6 years, 37% mild cognitive impairment (MCI), 33% female] underwent lumbar puncture to obtain CSF at study entry and serial multimodal 3T brain magnetic resonance imaging over a 7‐year follow‐up period (mean = 5.4 years). Enzyme‐linked immunosorbent assays quantified CSF Aβ42 and p‐tau181. Pseudo‐continuous arterial spin‐labeling captured CBF in total and lobar grey matter regions of interest (ROI). Linear mixed‐effects models related biomarker x time to longitudinal CBF variables adjusting for baseline age and cognitive status, sex, race/ethnicity, education, Framingham Stroke Risk Profile (minus age), ROI volume, APOE‐ε4 status, and time. Models were repeated testing a cognitive status x biomarker x time interaction term.ResultsIn main effect models, neither CSF Aβ42 (p‐values&gt;0.31) nor p‐tau (p‐values&gt;0.28) related to CBF outcomes. Aβ42 did not interact with cognitive status on CBF outcomes (p‐values&gt;0.37), but p‐tau interacted with baseline cognitive status on longitudinal frontal, temporal, parietal, occipital, and total grey matter CBF trajectories (p‐values&lt;0.005). Among cognitively unimpaired participants, higher p‐tau was associated with slower reductions in frontal (β = 0.01, p = 0.03), parietal (β = 0.01, p = 0.04), occipital (β = 0.01, p = 0.02), and total grey matter CBF (β = 0.01, p = 0.04). Among individuals with MCI, higher p‐tau was associated with faster reductions in frontal (β = ‐0.03, p = 0.008), temporal (β = ‐0.02, p = 0.01), parietal (β = ‐0.04, p = 0.002), occipital (β = ‐0.03, p = 0.0004), and total grey matter CBF (β = ‐0.03, p = 0.005).ConclusionsResults linking CSF p‐tau to CBF decline in MCI support the theory that grey matter hypoperfusion is a later‐stage event tied to neurofibrillary tangle pathology. Associations between higher p‐tau and slower rates of CBF decline among cognitively unimpaired individuals warrants further investigation. Funding: R01‐AG034962, K24‐AG046373, F31‐AG079640, T32‐AG058524, P20‐AG068082

Cardiac radiation improves ventricular function in mice and humans with cardiomyopathy.

Rapidly dividing cells are more sensitive to radiation therapy (RT) than quiescent cells. In the failing myocardium, macrophages and fibroblasts mediate collateral tissue injury, leading to progressive myocardial remodeling, fibrosis, and pump failure. Because these cells divide more rapidly than cardiomyocytes, we hypothesized that macrophages and fibroblasts would be more susceptible to lower doses of radiation and that cardiac radiation could therefore attenuate myocardial remodeling. In three independent murine heart failure models, including models of metabolic stress, ischemia, and pressure overload, mice underwent 5 Gy cardiac radiation or sham treatment followed by echocardiography. Immunofluorescence, flow cytometry, and non-invasive PET imaging were employed to evaluate cardiac macrophages and fibroblasts. Serial cardiac magnetic resonance imaging (cMRI) from patients with cardiomyopathy treated with 25 Gy cardiac RT for ventricular tachycardia (VT) was evaluated to determine changes in cardiac function. In murine heart failure models, cardiac radiation significantly increased LV ejection fraction and reduced end-diastolic volume vs. sham. Radiation resulted in reduced mRNA abundance of B-type natriuretic peptide and fibrotic genes, and histological assessment of the LV showed reduced fibrosis. PET and flow cytometry demonstrated reductions in pro-inflammatory macrophages, and immunofluorescence demonstrated reduced proliferation of macrophages and fibroblasts with RT. In patients who were treated with RT for VT, cMRI demonstrated decreases in LV end-diastolic volume and improvements in LV ejection fraction early after treatment. These results suggest that 5 Gy cardiac radiation attenuates cardiac remodeling in mice and humans with heart failure. NIH, ASTRO, AHA, Longer Life Foundation.

Novel TLR7 hemizygous variant in post-COVID-19 neurological deterioration: a case report with literature review

The neurological complications of coronavirus disease 2019 (COVID-19) can range from simple tremors and dystonia to features of encephalopathy. Toll-like receptor 7 (TLR7) belongs to a family of innate immune receptors responsible for viral RNA detection (such as SARS-CoV-2) and immune response initiation. TLR7 loss of function variants have been previously reported as genetic risk factors for severe COVID-19 infection in young patients with no comorbidities. In this case, we report a pediatric patient who developed severe long-term neurological deterioration following his COVID-19 infection. Presenting first to the clinic with episodic dystonia and finger spasticity, the patient’s condition rapidly deteriorated with a significant drop in the Glasgow Coma Scale (GCS). Despite improvement following initial treatment with rituximab and intravenous immunoglobulin, the patient’s symptoms relapsed, and GCS further dropped to 3/15. Serial brain magnetic resonance imaging scans revealed diffuse parenchymal atrophy, ventricular enlargement, and spinal cord thickening. Autoimmune investigations were negative but clinical whole genome sequencing prioritized four gene variants, the most significant of which was a novel frameshift null variant of the X chromosomal TLR7 gene (c.1386_1389dup, p.[His464Ilefs*7]). This case illustrates a role for TLR7 in long-term COVID-19 complications and highlights that TLR7 deficiency in the future may be addressed as a therapeutic measure.

Continuous time-resolved estimated synthetic 4D-CTs for dose reconstruction of lung tumor treatments at a 0.35 T MR-linac

Objective. To experimentally validate a method to create continuous time-resolved estimated synthetic 4D-computed tomography datasets (tresCTs) based on orthogonal cine MRI data for lung cancer treatments at a magnetic resonance imaging (MRI) guided linear accelerator (MR-linac). Approach. A breathing porcine lung phantom was scanned at a CT scanner and 0.35 T MR-linac. Orthogonal cine MRI series (sagittal/coronal orientation) at 7.3 Hz, intersecting tumor-mimicking gelatin nodules, were deformably registered to mid-exhale 3D-CT and 3D-MRI datasets. The time-resolved deformation vector fields were extrapolated to 3D and applied to a reference synthetic 3D-CT image (sCTref), while accounting for breathing phase-dependent lung density variations, to create 82 s long tresCTs at 3.65 Hz. Ten tresCTs were created for ten tracked nodules with different motion patterns in two lungs. For each dataset, a treatment plan was created on the mid-exhale phase of a measured ground truth (GT) respiratory-correlated 4D-CT dataset with the tracked nodule as gross tumor volume (GTV). Each plan was recalculated on the GT 4D-CT, randomly sampled tresCT, and static sCTref images. Dose distributions for corresponding breathing phases were compared in gamma (2%/2 mm) and dose–volume histogram (DVH) parameter analyses. Main results. The mean gamma pass rate between all tresCT and GT 4D-CT dose distributions was 98.6%. The mean absolute relative deviations of the tresCT with respect to GT DVH parameters were 1.9%, 1.0%, and 1.4% for the GTV D 98%, D 50%, and D 2%, respectively, 1.0% for the remaining nodules D 50%, and 1.5% for the lung V 20Gy. The gamma pass rate for the tresCTs was significantly larger (p < 0.01), and the GTV D 50% deviations with respect to the GT were significantly smaller (p < 0.01) than for the sCTref. Significance. The results suggest that tresCTs could be valuable for time-resolved reconstruction and intrafractional accumulation of the dose to the GTV for lung cancer patients treated at MR-linacs in the future.

A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes.

Background People with cystic fibrosis (CF) can experience recurrent chest infections, pancreatic exocrine insufficiency and gastrointestinal symptoms. New cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs improve lung function but gastrointestinal effects are unclear. We aimed to see if a CFTR modulator (tezacaftor-ivacaftor,TEZ/IVA) improves gastrointestinal outcomes in CF. Methods We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (2019-2020) at Nottingham University Hospitals. The effects of TEZ/IVA on gut physiology were measured using MRI. Participants were randomly assigned to treatment sequences AB or BA (A:TEZ/IVA, B:placebo, each 28 days), with a 28-day washout period. Participants had serial MRI scans at baseline and after 19-23 days of each treatment. Due to the COVID-19 pandemic, a protocol amendment allowed for observer-blind comparisons prior to and during TEZ/IVA. In such cases, participants were not blind to the treatment but researchers remained blind. The primary outcome was oro-caecal transit time (OCTT). Secondary outcomes included MRI metrics, symptoms and stool biomarkers. Results We randomised 13 participants. Before the COVID-19 pandemic 8 participants completed the full protocol and 1 dropped out. The remaining 4 participants followed the amended protocol. There were no significant differences between placebo and TEZ/IVA for OCTT (TEZ/IVA &gt;360minutes [225,&gt;360] vs. placebo 330minutes [285,&gt;360], p=0.8) or secondary outcomes. There were no adverse events. Conclusions Our data contribute to a research gap in the extra-pulmonary effects of CFTR modulators. We found no effect after TEZ/IVA on MRI metrics of gut function, GI symptoms or stool calprotectin. Effects might be detectable with larger studies, longer treatment or more effective CFTR modulators. ClinicalTrials.gov registration NCT04006873 (02/07/2019)

Association of Coronary Collaterals and Myocardial Salvage Measured by Serial Cardiac Magnetic Resonance Imaging after Acute Myocardial Infarction.

Coronary collateral flow in angiography has been linked with lower mortality rates in patients with coronary artery disease. However, the relevance of the underlying mechanism is sparse. Therefore, we tested the hypothesis that in patients with acute myocardial infarction (AMI), relevant coronary collateral flow is associated with more salvaged myocardium and lower risk of developing heart failure. Patients with first AMI who received a percutaneous coronary intervention within 24 h after symptom onset were classified visually by assigning a Cohen-Rentrop Score (CRS) ranging between 0 (no collaterals) and 3 (complete retrograde filling of the occluded vessel). All 36 patients included in the analysis underwent cardiac magnetic resonance examination within 3 to 5 days after myocardial infarction and after 12 weeks. Patients with relevant collateral flow (CRS 2-3) to the infarct-related artery had significantly smaller final infarct size compared to those without (7 ± 4% vs. 20 ± 12%, p < 0.001). In addition, both groups showed improvement in left ventricular ejection fraction early after AMI, whereas the recovery was greater in CRS 2-3 (+8 ± 5% vs. +3 ± 5%, p = 0.015). In patients with first AMI, relevant collateral flow to the infarct-related artery was associated with more salvaged myocardium at 12 weeks, translating into greater improvement of systolic left ventricular function. The protective effect of coronary collaterals and the variance of infarct location should be further investigated in larger studies.

Quantitative Assessment of Calf Muscle Volume, Strength, and Quality After Achilles Tendon Rupture Repair: A 1-Year Prospective Follow-up Study

Background: A number of studies have reported that calf muscle atrophy is a common long-term problem after Achilles tendon repair; however, there is still a lack of data concerning early postoperative morphological changes in the calf muscle after surgery. Purpose: To investigate changes over time in calf muscle volume and fatty degeneration during 1 year after Achilles tendon repair. Study Design: Cohort study; Level of evidence, 2. Methods: A prospective 1-year serial magnetic resonance imaging study was carried out with 20 patients who underwent tendon repair for unilateral acute Achilles tendon rupture. The magnetic resonance imaging assessment in addition to clinical and functional evaluations was performed at 1, 3, 6, and 12 months after surgery. The muscle volume of the medial and lateral gastrocnemius, soleus, and flexor hallucis longus (FHL) and fatty degeneration of the medial and lateral gastrocnemius and soleus were measured for the calf muscles, and the relative volume and fatty degeneration changes in the affected leg compared with the healthy contralateral leg were calculated as a percentage ([injured/healthy control] × 100) to assess structural changes over time. Results: Muscle volumes of the medial gastrocnemius, lateral gastrocnemius, soleus, and FHL were 92.3%, 92.8%, 84.6%, and 95.9% at 12 months after surgery, respectively. Medial and lateral gastrocnemius and FHL muscle volumes improved over time and recovered to almost equal to that of the healthy side at 12 months after surgery. The soleus muscle volume did not recover significantly over time and was statistically significantly smaller than that of the healthy side at 12 months (P = .029). Fatty degeneration rates of the medial gastrocnemius, lateral gastrocnemius, and soleus were 118.2%, 113.9% and 121.1% at 12 months after surgery, respectively. Fatty degeneration of the medial and lateral gastrocnemius did not change significantly, but there was a statistically significant increase in fatty degeneration of the soleus over time (P < .001). Conclusion: Within the triceps surae muscle, the soleus was the most negatively affected by injury and repair for both muscle volume and fatty degeneration. Postoperative management to recover the soleus muscle function before a return to sporting activities should be considered in the future.

NIMG-25. CLINICAL FEASIBILITY OF AI-BASED T2 FLAIR SEGMENTATION FOR DETECTION OF PROGRESSION IN NON-ENHANCING LOWER GRADE GLIOMA

Abstract Radiological assessment of progression in patients with non-enhancing lower grade gliomas (LrGG: grade 2 and 3) is primarily based on increase in lesion size on anatomical T2-weighted fluid-attenuated inversion recovery (T2 FLAIR) magnetic resonance imaging (MRI) sequences. We evaluated whether an AI-based method could be used routinely as part of patient care to assist in detecting non-enhancing glioma progression. The software offers the ability for real-time quality control and editing, choice of baseline exam and threshold for progression, and shows 3D image segmentations side-by-side with lesion volume graphs. The model was trained to create T2 FLAIR abnormality segmentations. The 515 training images included pre-surgical scans of newly diagnosed and recurrent patients, and post-surgical surveillance scans of patients. Clara Deploy was used for inference and to handle communication between PACS and an XNAT server, where results were stored and displayed. Following RANO criteria, lesions were marked as ‘progressed’ if volume changes were larger than 40% between baseline and the MRI of interest. The 124 AI-based segmentation model test volumes were compared to manual segmentation volumes, and achieved a mean DICE score of 0.87 ± 0.20. The sensitivity and specificity of the RANO progression assessment based on the model was compared with RANO progression assessment based on manual segmentation in 16 patients (6 serial MRIs each), with 85% sensitivity, 82% specificity. This work presents the first steps toward clinical deployment of AI-based real-time quantitative detection of LrGG progression by RANO criteria. This quantitative assessment provides supplementary information to the radiologist and can be shared with the patient’s neuro-oncologist, neurosurgeon, and other clinical team members for consideration in treatment planning.

RADT-51. RADIATION-INDUCED CEREBRAL CONTRAST ENHANCEMENTS STRONGLY SHARE RISK FACTORS WITH STROKE

Abstract BACKGROUND AND PURPOSE Radiation-induced cerebral contrast enhancements (RICE) are feared because frequent and potentially health-threatening. Risk factors are badly understood. Better understanding of RICE risk factors is critical to better face its risks by adapting therapy in the first place or patient care during follow-up. MATERIALS AND METHODS We analyzed consecutive 235 patients treated with proton radiotherapy (PRT; 54Gy RBE) for LGG from 2010 to 2020 and followed with serial clinical exams and magnetic resonance imaging for in median 5.6 years. RESULTS The risk of RICE was significantly higher in patients with vascular risk factors (VRF) (p = 0.02). Especially age ≥50 years (vs. adults &amp;lt;50 years: two-fold risk; p = 0.02), hypertension (three-fold risk; p = 0.0001) and diabetes (6.7-fold risk; p = 0.007) were shown to be clearly associated to RICE occurrence. Dyslipidemia (2.4-fold), overweight (1.3-fold) and smoking (1.3-fold) was also more frequently observed in the cohort that developed RICE. History of previous stroke went along with a 1.7-fold risk for RICE but threshold for significance was not reached. If RICE occurred, Bevacizumab treatment was two-fold more frequently needed in the cohort with VRF, but RICE prognosis did not differ relevantly between the RICE subcohort with and without VRF. CONCLUSIONS These data firstly demonstrate that RICE strongly share risk factors with ischemic stroke which further enhances our vague understanding of multifactorial pathophysiology and opportunities of tackling RICE. Classical vascular risk factors, especially age, hypertension and diabetes correlated strongly with RICE risk. Risk-adapted screening and therapy can be directly derived from this data.

Abstract 11536: Cardiac Magnetic Resonance Imaging Paralleled Recurrent Pericarditis Clinical Response to Rilonacept Treatment Over 18 Months: A RHAPSODY Subgroup Analysis

Introduction: Rilonacept treatment in RHAPSODY resolved active pericarditis recurrences, and long-term treatment led to sustained risk reduction. Prior analysis linked greater baseline Late Gadolinium Enhancement (LGE), with more rapid recurrence upon rilonacept suspension after 12 weeks of treatment. Serial cardiac magnetic resonance (CMR) imaging (T2-STIR, LGE) enabled longitudinal assessment for tracking clinical improvement, guiding decision-making, and predicting patient outcomes after treatment cessation. Methods: At the long-term extension (LTE) 18-month decision milestone (18MDM), investigators chose, based on clinical status, to continue rilonacept, suspend rilonacept/observe, or discontinue the LTE. An imaging core lab blinded to clinical data measured pericardial thickness and graded pericardial edema (T2-STIR) and LGE at baseline and 18MDM. Pericarditis recurrence was assessed clinically following rilonacept suspension. Results: Baseline and 18MDM CMRs were available for 13 patients. Reductions in pericardial thickness, T2-STIR, and LGE from baseline to 18MDM while on treatment are provided in Figure . CMRs were obtained in 7/8 patients suspending rilonacept at 18MDM: LGE was none/trace, and T2-STIR was negative; yet, 5/7 (71%) had pericarditis recurrence within 1-4 months of rilonacept suspension despite prophylactic colchicine (n=2). Conclusions: Continued clinical improvement during prolonged rilonacept treatment corresponded with improvement on CMR, including reduced pericardial thickness, resolution of pericardial edema on T2-STIR, and resolution of LGE. Negative/trace LGE at 18MDM while on treatment did not predict absence of pericarditis recurrence upon subsequent rilonacept suspension in this size-limited subgroup. Larger prospective studies examining CMR parameters in guiding RP treatment duration decisions and informing associated clinical outcomes are warranted.

Time-Dependent Change in Carpal Tunnel Cross-Sectional Area and Transverse Carpal Ligament Thickness Using Serial Magnetic Resonance Imaging Studies—An Anatomical Study

Idiopathic carpal tunnel syndrome (CTS) is a common compressive neuropathy. Aging and female sex are risk factors, but the reasons are unclear. The purpose of this study was to evaluate whether identifiable radiographic changes resulting in a decrease in carpal tunnel area (CTA) over time exist. A database search of a multicenter, academic, tertiary institution from 1998 to 2021 identified 433 patients with serial wrist magnetic resonance images (MRI) at least 5 years apart. Fifty-six met the inclusion criteria with adequate films to measure CTA and transverse carpal ligament (TCL) thickness at the same slice location-the carpal tunnel inlet, hook of the hamate, and carpal tunnel outlet-independently by two observers who were blinded to each other's measurements. Rates for the change in CTA and TCL thickness were calculated at all three locations. Thickness of the TCL increased, whereas that of the CTA decreased over time. Inlet CTA decreased by 0.9 mm2 per year (95% CI: 0.34-1.5), outlet CTA decreased by 1.8 mm2 per year (95% CI: 1.2-2.5), and CTA at the hook of the hamate decreased by 1.6 mm2 per year (95% CI: 1.0-2.0 per year). The TCL thickened by 0.02 mm per year at all three sections. Taller patients had a decreased rate of CTA loss. In this select cohort, TCL thickened and CTA decreased with time. TCL thickening accounted for about half of the variation in CTA, suggesting that this is a possible contributor to this change. Hypertrophy of the carpal tunnel floor may account for the remaining variation in CTA. The question of whether these results are reliable and generalizable to the general population, or a major influence in the pathophysiology of CTS, is unknown. Small decreases in CTA and thickening of the TCL occur with aging. Whether this is a contributing factor in the development of CTS requires further study.

OTHER-11 DEMENTIA AND EPILEPSY REVERSED SUCCESSFULLY THROUGH STAGED EMBOLISATION OF A SYMPTOMATIC HYPERVASCULAR PARAGANGLIOMA : A CASE REPORT

Abstract INTRODUCTION Paragangliomas (PGs) are rare neuroendocrine tumours that can arise from parasympathetic glossopharyngeal and vagus nerves. Atypical presentations involving seizures and dementia can occur due to excessive catecholamine release. Physiological intracranial arteriovenous fistulae (AVF) can occur concurrently due to increased vascularity, especially in the cavernous and sigmoid sinuses. METHODS We present a case of a patient who developed a highly vascular AVF from an ipsilateral glomus jugulare PG, presenting with rapidly progressive but reversible dementia and epilepsy. CASE: A 64-year-old lady presented on several occasions with new-onset stereotyped episodes of confusional dysphasia suggestive of seizures, confirmed on electroencephalography. Further history revealed two years of progressive deafness and imbalance, and one year of increasing forgetfulness and executive dysfunction, which had deteriorated rapidly in the period of the patient's current presentations. Montreal cognitive assessment (MoCA) score was 21/30 at baseline (normal score &amp;gt;25/30), and she had no lateralising signs. Serial brain magnetic resonance imaging (MRI) revealed progressively worsening vasculopathic white matter hyper-intensities (WMHs). Eventual MR angiography showed a 14x22×23mm right glomus jugulotympanicum PG with numerous feeding arteries, and associated multiple AVFs (Cognard grade III). She was initially managed with anti-seizure medications and then discussed in our multidisciplinary neurosciences meeting. The patient underwent staged right glomus jugulare embolization over several weeks. Her cognitive function gradually improved, and at three months she had fully returned to normal functioning with a MoCA of 30/30 and no residual neurological deficit. The WMHs disappeared on follow-up MRI scans. CONCLUSION Our case highlights a rare clinical presentation of dementia and seizures from a right glomus jugulare PG with associated AVF. Multidisciplinary involvement was key in excluding other causes, and definitive treatment of the PG led to complete reversal of the patient’s dementia.