Lung apical findings in coronavirus disease (COVID-19) infection on neck and cervical spine CT.

PURPOSE: To evaluate the prevalence and features of lung apical findings on neck and cervical spine CTs performed in patients with COVID-19. METHODS: This was a retrospective, IRB-approved study performed at a large academic hospital in the USA. Between March 3, 2020, and May 6, 2020, 641 patients with COVID-19 infection diagnosed by RT-PCR received medical care at our institution. A small cohort of patients with COVID-19 infection underwent neck or cervical spine CT imaging for indications including stroke, trauma, and neck pain. The lung apices included in the field of view on these CT scans were reviewed for the presence of findings suspicious for COVID-19 pneumonia, including ground-glass opacities, consolidation, or crazy-paving pattern. The type and frequency of these findings were recorded and correlated with clinical information including age, gender, and symptoms. RESULTS: Thirty-four patients had neck or spine CTs performed before or concurrently with a chest CT. Of this group, 17 (50%) had unknown COVID-19 status at the time of neck or spine imaging and 10 (59%) of their CT studies had findings in the lung apices consistent with COVID-19 pneumonia. CONCLUSION: Lung apical findings on cervical spine or neck CTs consistent with COVID-19 infection are common and may be encountered on neuroimaging performed for non-respiratory indications. For these patients, the emergency radiologist may be the first physician to suspect underlying COVID-19 infection.

Diagnostic evaluation of deep learning accelerated lumbar spine MRI.

BACKGROUND AND PURPOSE: Deep learning (DL) accelerated MR techniques have emerged as a promising approach to accelerate routine MR exams. While prior studies explored DL acceleration for specific lumbar MRI sequences, a gap remains in comprehending the impact of a fully DL-based MRI protocol on scan time and diagnostic quality for routine lumbar spine MRI. To address this, we assessed the image quality and diagnostic performance of a DL-accelerated lumbar spine MRI protocol in comparison to a conventional protocol. METHODS: We prospectively evaluated 36 consecutive outpatients undergoing non-contrast enhanced lumbar spine MRIs. Both protocols included sagittal T1, T2, STIR, and axial T2-weighted images. Two blinded neuroradiologists independently reviewed images for foraminal stenosis, spinal canal stenosis, nerve root compression, and facet arthropathy. Grading comparison employed the Wilcoxon signed rank test. For the head-to-head comparison, a 5-point Likert scale to assess image quality, considering artifacts, signal-to-noise ratio (SNR), anatomical structure visualization, and overall diagnostic quality. We applied a 15% noninferiority margin to determine whether the DL-accelerated protocol was noninferior. RESULTS: No significant differences existed between protocols when evaluating foraminal and spinal canal stenosis, nerve compression, or facet arthropathy (all p > .05). The DL-spine protocol was noninferior for overall diagnostic quality and visualization of the cord, CSF, intervertebral disc, and nerve roots. However, it exhibited reduced SNR and increased artifact perception. Interobserver reproducibility ranged from moderate to substantial (κ = 0.50-0.76). CONCLUSION: Our study indicates that DL reconstruction in spine imaging effectively reduces acquisition times while maintaining comparable diagnostic quality to conventional MRI.

Clinical Evaluation of a 2-Minute Ultrafast Brain MR Protocol for Evaluation of Acute Pathology in the Emergency and Inpatient Settings.

BACKGROUND AND PURPOSE: The use of MR imaging in emergency settings has been limited by availability, long scan times, and sensitivity to motion. This study assessed the diagnostic performance of an ultrafast brain MR imaging protocol for evaluation of acute intracranial pathology in the emergency department and inpatient settings. MATERIALS AND METHODS: Sixty-six adult patients who underwent brain MR imaging in the emergency department and inpatient settings were included in the study. All patients underwent both the reference and the ultrafast brain MR protocols. Both brain MR imaging protocols consisted of T1-weighted, T2/T2*-weighted, FLAIR, and DWI sequences. The ultrafast MR images were reconstructed by using a machine-learning assisted framework. All images were reviewed by 2 blinded neuroradiologists. RESULTS: The average acquisition time was 2.1 minutes for the ultrafast brain MR protocol and 10 minutes for the reference brain MR protocol. There was 98.5% agreement on the main clinical diagnosis between the 2 protocols. In head-to-head comparison, the reference protocol was preferred in terms of image noise and geometric distortion (P < .05 for both). The ultrafast ms-EPI protocol was preferred over the reference protocol in terms of reduced motion artifacts (P < .01). Overall diagnostic quality was not significantly different between the 2 protocols (P > .05). CONCLUSIONS: The ultrafast brain MR imaging protocol provides high accuracy for evaluating acute pathology while only requiring a fraction of the scan time. Although there was greater image noise and geometric distortion on the ultrafast brain MR protocol images, there was significant reduction in motion artifacts with similar overall diagnostic quality between the 2 protocols.

Targeting hypoxia-inducible factors with 32-134D safely and effectively treats diabetic eye disease in mice.

Many patients with diabetic eye disease respond inadequately to anti-VEGF therapies, implicating additional vasoactive mediators in its pathogenesis. We demonstrate that levels of angiogenic proteins regulated by HIF-1 and -2 remain elevated in the eyes of people with diabetes despite treatment with anti-VEGF therapy. Conversely, by inhibiting HIFs, we normalized the expression of multiple vasoactive mediators in mouse models of diabetic eye disease. Accumulation of HIFs and HIF-regulated vasoactive mediators in hyperglycemic animals was observed in the absence of tissue hypoxia, suggesting that targeting HIFs may be an effective early treatment for diabetic retinopathy. However, while the HIF inhibitor acriflavine prevented retinal vascular hyperpermeability in diabetic mice for several months following a single intraocular injection, accumulation of acriflavine in the retina resulted in retinal toxicity over time, raising concerns for its use in patients. Conversely, 32-134D, a recently developed HIF inhibitor structurally unrelated to acriflavine, was not toxic to the retina, yet effectively inhibited HIF accumulation and normalized HIF-regulated gene expression in mice and in human retinal organoids. Intraocular administration of 32-134D prevented retinal neovascularization and vascular hyperpermeability in mice. These results provide the foundation for clinical studies assessing 32-134D for the treatment of patients with diabetic eye disease.

PAI-1 is a vascular cell-specific HIF-2-dependent angiogenic factor that promotes retinal neovascularization in diabetic patients.

For patients with proliferative diabetic retinopathy (PDR) who do not respond adequately to pan-retinal laser photocoagulation (PRP) or anti-vascular endothelial growth factor (VEGF) therapies, we hypothesized that vascular cells within neovascular tissue secrete autocrine/paracrine angiogenic factors that promote disease progression. To identify these factors, we performed multiplex ELISA angiogenesis arrays on aqueous fluid from PDR patients who responded inadequately to anti-VEGF therapy and/or PRP and identified plasminogen activator inhibitor-1 (PAI-1). PAI-1 expression was increased in vitreous biopsies and neovascular tissue from PDR eyes, limited to retinal vascular cells, regulated by the transcription factor hypoxia-inducible factor (HIF)-2α, and necessary and sufficient to stimulate angiogenesis. Using a pharmacologic inhibitor of HIF-2α (PT-2385) or nanoparticle-mediated RNA interference targeting Pai1, we demonstrate that the HIF-2α/PAI-1 axis is necessary for the development of retinal neovascularization in mice. These results suggest that targeting HIF-2α/PAI-1 will be an effective adjunct therapy for the treatment of PDR patients.

Expression of the angiogenic mediator, angiopoietin-like 4, in the eyes of patients with proliferative sickle retinopathy.

The recent success of therapies directly targeting the angiogenic mediator, vascular endothelial growth factor (VEGF), for the treatment of proliferative diabetic retinopathy has encouraged clinicians to extend the use of anti-VEGF therapies for the treatment of another ischemic retinal vascular disease, proliferative sickle cell retinopathy (PSR), the most common cause of irreversible blindness in patients with sickle cell disease. However, results from case reports evaluating anti-VEGF therapies for PSR have been mixed. This highlights the need to identify alternative therapeutic targets for the treatment of retinal neovascularization in sickle cell patients. In this regard, angiopoietin-like 4 (ANGPTL4) is a novel angiogenic factor regulated by the transcription factor, hypoxia-inducible factor 1, the master regulator of angiogenic mediators (including VEGF) in ischemic retinal disease. In an effort to identify alternative targets for the treatment of sickle cell retinopathy, we have explored the expression of ANGPTL4 in the eyes of patients with PSR. To this end, we examined expression and localization of ANGPTL4 by immunohistochemistry in autopsy eyes from patients with known PSR (n = 5 patients). Complementary studies were performed using enzyme-linked immunosorbent assays in aqueous (n = 8; 7 patients, 2 samples from one eye of same patient) and vitreous (n = 3 patients) samples from a second group of patients with active PSR. We detected expression of ANGPTL4 in neovascular tissue and in the ischemic inner retina in PSR, but not control, eyes. We further observed elevated expression of ANGPTL4 in the aqueous and vitreous of PSR patients compared to controls. These results suggest that ANGPTL4 could contribute to the development of retinal neovascularization in sickle cell patients and could therefore be a therapeutic target for the treatment of PSR.

Lack of Evidence for Vasoactive and Inflammatory Mediators in the Promotion of Macular Edema Associated with Epiretinal Membranes.

The development of symptoms in patients with epiretinal membranes (ERMs) often corresponds with the accumulation of interstitial fluid in the retina [i.e., the development of macular edema, (ME)]. To explore the potential value of pharmacologic therapeutic options to treat ME in patients with ERMs, we examine here the expression of vasoactive and inflammatory mediators in the vitreous of patients with idiopathic ERMs. We observed that vitreous concentrations of classic vasoactive factors (e.g., vascular endothelial growth factor) were similar in ERM patients with ME compared to controls. Using an array assessing the expression of 102 inflammatory cytokines we similarly did not observe a marked difference in cytokine expression in the vitreous of most ERM patients with ME compared to control patients. While the array data did implicate a group of inflammatory cytokines that were elevated in a subset of ERM patients who had severe ME (central subfield thickness ≥450 µm on spectral domain optical coherence tomography), expression of 3 of these inflammatory cytokines, all previously implicated in the promotion of ME in ischemic retinal disease, were not elevated by quantitative enzyme-linked immunosorbent assay. We conclude that therapies modulating vasoactive mediators or inflammatory cytokines may not affect ME in ERM patients.