Ultra-deep through-skull mouse brain imaging via the combination of skull optical clearing and three-photon microscopy

Optical microscopy has enabled in vivo monitoring of brain structures and functions with high spatial resolution. However, the strong optical scattering in turbid brain tissue and skull impedes the observation of microvasculature and neuronal structures at large depth. Herein, we proposed a strategy to overcome the influence induced by the high scattering effect of both skull and brain tissue via the combination of skull optical clearing (SOC) technique and thee-photon fluorescence microscopy (3PM). The Visible-NIR-II compatible Skull Optical Clearing Agents (VNSOCA) we applied reduced the skull scattering and water absorption in long wavelength by refractive index matching and H2O replacement to D2O respectively. 3PM with the excitation in the 1300-nm window reached 1.5 mm cerebrovascular imaging depth in cranial window. Combining the two advanced technologies together, we achieved so far the largest cerebrovascular imaging depth of 1 mm and neuronal imaging depth of >700 μm through intact mouse skull. Dual-channel through-skull imaging of both brain vessels and neurons was also successfully realized, giving an opportunity of non-invasively monitoring the deep brain structures and functions at single-cell level simultaneously.

Carotid Artery Stenting

Purpose of The ReviewTo examine current understanding of diverse etiologies of extracranial carotid disease, including clinical and imaging manifestations as well as treatment approaches.Recent FindingsIncreasing availability of advanced cerebrovascular imaging modalities continues to elucidate atherosclerotic and nonatherosclerotic carotid steno-occlusive disease as a common culprit of cerebral ischemia. Individualized treatment strategies targeting each etiologic subset would optimize preventive measures and minimize recurrence of cerebral ischemia.SummaryIschemic stroke is a prominent cause of mortality and long-term disability worldwide. The magnified effect of carotid disease warrants constant and close inspection.

The role of noninvasive imaging in the diagnostic workup for pulsatile tinnitus

Objective We sought to assess the diagnostic yield of advanced noninvasive imaging in the evaluation of patients with pulsatile tinnitus. Background Pulsatile tinnitus can be caused by high-risk cerebrovascular pathologies such as arteriovenous fistulae. The role of advanced noninvasive imaging, including magnetic resonance angiography and magnetic resonance venography, in the diagnostic evaluation of pulsatile tinnitus is not well defined. Design and methods We performed a retrospective cohort study of patients presenting for outpatient diagnostic evaluation of pulsatile tinnitus from January 2018 to March 2020 at Weill Cornell Medicine. Patients with non-pulsatile tinnitus and established etiologic diagnoses were excluded. Systematic chart abstraction was summarized using standard descriptive statistics. Univariate logistic regression was used to identify factors associated with nondiagnostic noninvasive imaging. Results A total of 187 patients (139 (74.3%) women) took part in this study, with a mean age of 48.6 years (standard deviation ( SD) = 15.5 years) and a mean body mass index (BMI) of 26.9 kg/m2 ( SD = 6.1 kg/m2). Of the 187 patients, 121 (64.7%) underwent exclusively noninvasive imaging, and 66 (35.3%) patients also had digital subtraction angiography (DSA). In patients who had exclusively noninvasive imaging, 62 (51.2%) patients received a diagnosis. In patients who underwent noninvasive and DSA imaging, 14 (21.2%) patients received a diagnosis based on DSA. Patients who were older at symptom onset (odds ratio (OR) = 1.05; 95% confidence interval (CI) 1.01–1.09) and those with a lower BMI (OR = 0.88, 95% CI 0.77–0.98) were more likely to have nondiagnostic noninvasive imaging. Conclusion Noninvasive cerebrovascular imaging often uncovers the etiology of pulsatile tinnitus. DSA remains useful for additional evaluation for patients with specific associated features.

Abstract P588: A Rare RNF213 Variant is Associated With Moyamoya Disease in an African American Family

Objective: To investigate potential genetic susceptibility for moyamoya disease (MMD) in an African American family. Methods: A young girl with MMD (proband), her father and paternal half-brother underwent cerebrovascular imaging with MRI and MRA. Cerebral angiography was also performed on the girl and her father. Genetic analysis of the MMD susceptibility gene RNF213 was conducted on all three relatives, while ACTA2 gene was analysed in the proband only. Results: The proband presented with pseudobulbar affect and chorea, then subsequently had a right hemispheric ischaemic stroke and rapid, ultimately fatal clinical decline. Detailed family history raised suspicion for familial MMD and investigation of her relatives. Her father had a small haemorrhagic thalamic stroke without residual neurologic deficits; a clinically silent ischaemic infarct was incidentally discovered on neuroimaging. He remains clinically stable despite slowly progressive disease on imaging. Her brother is neurologically intact and has normal cerebrovascular imaging to date. They are all heterozygous for the rare Arg4131Cys variant in RNF213. They are the first Black people and only the 3rd, 4th and 5th people in the world known to harbour this variant. MMD was confirmed in the girl and her father with cerebral angiogram. Conclusions: This study illuminates the clinical and genetic complexity of familial MMD. It underscores the importance of genetic testing and surveillance cerebrovascular imaging even in asymptomatic relatives of probands with MMD. Although the clinical significance of Arg4131Cys remains unclear, modest variant-disease segregation in this family is consistent with a growing body of evidence supporting its probable pathogenicity. Furthermore, our study illustrates its wide phenotypic spectrum, from asymptomatic carrier to late presenting, mild disease to fulminant, rapidly fatal childhood disease. To our knowledge, this is also the first report of heritable MMD in a Black family. We demonstrate the value of considering diseases more predominant in one specific ancestry when evaluating patients from other ethnic backgrounds. Finally, we highlight the importance of racially and ethnically diverse participants in biomedical research.

4D flow MRI for non-invasive measurement of blood flow in the brain: A systematic review

The brain’s vasculature is essential for brain health and its dysfunction contributes to the onset and development of many dementias and neurological disorders. While numerous in vivo imaging techniques exist to investigate cerebral haemodynamics in humans, phase-contrast magnetic resonance imaging (MRI) has emerged as a reliable, non-invasive method of quantifying blood flow within intracranial vessels. In recent years, an advanced form of this method, known as 4D flow, has been developed and utilised in patient studies, where its ability to capture complex blood flow dynamics within any major vessel across the acquired volume has proved effective in collecting large amounts of information in a single scan. While extremely promising as a method of examining the vascular system’s role in brain-related diseases, the collection of 4D data can be time-consuming, meaning data quality has to be traded off against the acquisition time. Here, we review the available literature to examine 4D flow’s capabilities in assessing physiological and pathological features of the cerebrovascular system. Emerging techniques such as dynamic velocity-encoding and advanced undersampling methods, combined with increasingly high-field MRI scanners, are likely to bring 4D flow to the forefront of cerebrovascular imaging studies in the years to come.