Low-field 0.55 T MRI for assessment of pulmonary groundglass and fibrosis-like opacities: Inter-reader and inter-modality concordance.

PURPOSE: To evaluate detection and characterization of groundglass and fibrosis-like opacities imaged by non-contrast 0.55 Tesla MRI, and versus clinically-acquired chest CT images, in a cohort of post-Covid patients. MATERIALS AND METHODS: 64 individuals (26 women, mean age 53 ± 14 years, range 19-85) with history of Covid-19 pneumonia were recruited through a survivorship registry, with 106 non-contrast low-field 0.55 T cardiopulmonary MRI exams acquired from 9/8/2020-9/28/2021. MRI exams were obtained at an average interval of 9.5 ± 4.5 months from initial symptom report (range 1-18 months). Of these, 20 participants with 22 MRI exams had corresponding clinically-acquired CT chest imaging obtained within 30 days of MRI (average interval 18 ± 9 days, range 0-30). MR and CT images were reviewed and scored by two thoracic radiologists, for presence and extent of lung opacity by quadrant, opacity distribution, and presence versus absence of fibrosis-like subpleural reticulation and subpleural lines. Scoring was performed for each of four lung quadrants: right upper and middle lobe, right lower lobe, left upper lobe and lingula, and left lower lobe. Agreement between readers and modalities was assessed with simple and linear weighted Cohen's kappa (k) coefficients. RESULTS: Inter-reader concordance on CT for opacity presence, opacity extent, opacity distribution, and presence of subpleural lines and reticulation was 99%, 78%, 97%, 99%, and 94% (k 0.96, 0.86, 0.94, 0.97, 0.89), respectively. Inter-reader concordance on MR, among all 106 exams, for opacity presence, opacity extent, opacity distribution, and presence of subpleural lines and reticulation was 85%, 48%, 70%, 86%, and 76% (k 0.57, 0.32, 0.46, 0.47, 0.37), respectively. Inter-modality agreement between CT and MRI for opacity presence, opacity extent, opacity distribution, and presence subpleural lines and reticulation was 86%, 52%, 79%, 93%, and 76% (k 0.43, 0.63, 0.65, 0.80, 0.52). CONCLUSION: Low-field 0.55 T non-contrast MRI demonstrates fair to moderate inter-reader concordance, and moderate to substantial inter-modality agreement with CT, for detection and characterization of groundglass and fibrosis-like opacities.

A novel approach to percutaneous aortic thrombectomy.

Aortic mural thrombus in the absence of underlying aortic disease is rare and results in a risk of distant arterial embolization that can result in limb loss or other end organ damage. Current management involves open surgery, anticoagulation, and systemic thrombolysis; however, each carries inherent risks. We report the case of aortic thrombus with distal emboli in two patients, a 56-year-old man and a 68-year-old man, neither with underlying aortic pathology and both presenting with limb threatening ischemia. We performed percutaneous mechanical thrombectomy using the FlowTriever System (Inari Medical, Irvine, Calif) with successful removal of the aortic thrombus in both patients.

Furamidine Rescues Myotonic Dystrophy Type I Associated Mis-Splicing through Multiple Mechanisms.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant, CTG•CAG microsatellite expansion disease. Expanded CUG repeat RNA sequester the muscleblind-like (MBNL) family of RNA-binding proteins, thereby disrupting their normal cellular function which leads to global mis-regulation of RNA processing. Previously, the small molecule furamidine was shown to reduce CUG foci and rescue mis-splicing in a DM1 HeLa cell model and to rescue mis-splicing in the HSALR DM1 mouse model, but furamidine's mechanism of action was not explored. Here we use a combination of biochemical, cell toxicity, and genomic studies in DM1 patient-derived myotubes and the HSALR DM1 mouse model to investigate furamidine's mechanism of action. Mis-splicing rescue was observed in DM1 myotubes and the HSALR DM1 mouse with furamidine treatment. Interestingly, while furamidine was found to bind CTG•CAG repeat DNA with nanomolar affinity, a reduction in expanded CUG repeat transcript levels was observed in the HSALR DM1 mouse but not DM1 patient-derived myotubes. Further investigation in these cells revealed that furamidine treatment at nanomolar concentrations led to up-regulation of MBNL1 and MBNL2 protein levels and a reduction of ribonuclear foci. Additionally, furamidine was shown to bind CUG RNA with nanomolar affinity and disrupted the MBNL1 -CUG RNA complex in vitro at micromolar concentrations. Furamidine's likely promiscuous interactions in vitro and in vivo appear to affect multiple pathways in the DM1 mechanism to rescue mis-splicing, yet surprisingly furamidine was shown globally to rescue many mis-splicing events with only modest off-target effects on gene expression in the HSALR DM1 mouse model. Importantly, over 20% of the differentially expressed genes were shown to be returned, to varying degrees, to wild-type expression levels.