Brain Vascular Imaging Research Articles

Green Synthesis of Silver Nanoparticles Using <i>Citrus sinensis</i> Peels Assisted by Microwave Irradiation as a Contrast Agents for Computed Tomography Imaging

Contrast agents are extensively used to enhance the quality of images in computed tomography (CT) scans for brain exams, vascular imaging, and full-body imaging. Recent data indicate that iodine-based contrast agents have brief durations of blood circulation and may lead to harmful toxicity effects. This study aims to produce silver nanoparticles using environmentally friendly synthesis techniques facilitated by microwaves. The characteristics of nanoparticles have been studied using UV-vis, FTIR, XRD, and TEM techniques. The TEM analysis reveals that the silver nanoparticle has an average diameter of 9 nm and exhibits a spherical shape. The contrast-to-noise ratio (CNR) values of silver nanoparticles at 100, 150, and 200 mg/L concentrations are 35.79, 48.16, and 74.66, respectively. In comparison, iodine exhibits CNR values of 28.57, 34.69, and 48.56 at the same concentrations. The CNR values for tube currents of 140, 160, and 180 mA are 37.83, 44.98, and 48.26, respectively. In contrast, the CNR values in silver nanoparticles are 63.64, 75.32, and 81.67. The results obtained from the different concentrations and tube currents clearly demonstrate that silver nanoparticles have a higher CNR than iopamidol. Hence, silver nanoparticles have significant potential as contrast agents.

Molecularly engineered high-performance AIE luminogen for NIR-III excitable deep-brain three-photon fluorescence imaging

Three-photon microscopy (3PM) utilizing near-infrared-III (NIR-III) excitation has emerged as an effective technology for deep-tissue bioimaging. Within this domain, organic small molecules with aggregation-induced emission (AIE) property prove to be promising candidates as high-quality 3PM imaging agents because of their exceptional optical properties and the general merit of biocompatibility that most organic small molecules possess. However, due to the bidirectional effects of the intrinsic structure distortion of AIE luminogens (AIEgens) on the three-photon absorption cross section (σ3) and fluorescence quantum yield (η), two crucial factors that determine 3PM performances, the development of high-powered AIE-active 3PM probes with robust ησ3 remains a formidable challenge. In this work, by synergistically integrating multiple beneficial principles into the molecule design, an innovative AIE-active 3PM probe with a symmetrical quadrupole D–A–D architecture, namely TIT, was successfully constructed. Owing to the harmonized planarity and distortion, as well as strong D–A interaction within TIT, the as-prepared TIT nanoparticles (NPs) exhibited boosted ησ3 under 1665 nm NIR-III excitation. This breakthrough enabled brain vascular imaging at a remarkable depth of 1895 μm after craniotomy, thus positioning TIT among the top three organic 3PM probes in terms of imaging depth. In addition, successful hemodynamic imaging at a depth of 1200 μm within the mouse brain post-craniotomy was also accomplished. These achievements establish TIT NPs as highly promising probes for in vivo deep-brain three-photon imaging.

Atherosclerotic plaque characteristics in extracranial carotid artery may indicate closer association with white matter hyperintensities than intracranial arteries: A CARE-II study

PurposeThis study aimed to investigate the associations of atherosclerotic plaque characteristics in intracranial and extracranial carotid arteries with severity of white matter hyperintensities (WMHs) in symptomatic patients using magnetic resonance (MR) imaging. MethodPatients with cerebrovascular symptoms and carotid plaque were recruited from the cross-sectional, multicenter study of CARE-II. Luminal stenosis of intracranial and extracranial carotid arteries, carotid plaque compositional features, and WMHs were evaluated by brain structural and vascular MR imaging. The atherosclerotic plaque characteristics in intracranial and extracranial carotid arteries were compared between patients with and without moderate-to-severe WMHs (Fazekas score > 2), and their associations with severity of WMHs were analyzed using logistic regression. ResultsOf the recruited 622 patients (mean age, 58.7 ± 10.9 years; 422 males), 221 (35.5 %) had moderate-to-severe WMHs with higher prevalence of moderate-to-severe luminal stenosis (17.0 % vs. 10.4 %), intraplaque hemorrhage (15.7 % vs. 9.0 %), thin/ruptured fibrous cap (30.2 % vs. 20.4 %), calcification (44.4 % vs. 22.2 %) and lipid-rich necrotic core (63.8 % vs. 51.1 %) in carotid artery compared to those without (all P < 0.05). Multivariate logistic regression showed that carotid calcification (OR, 1.854; 95 % CI, 1.187–2.898; P = 0.007) was independently associated with moderate-to-severe WMHs after adjusting for confounding factors. No significant association was found between intracranial atherosclerotic stenosis and moderate-to-severe WMHs (P > 0.05). ConclusionCarotid atherosclerotic plaque features, particularly presence of calcification, were independently associated with severity of WMHs, but such association was not found in intracranial atherosclerotic stenosis, suggesting that carotid atherosclerotic plaque characteristics may have closer association with severity of WMHs compared to intracranial atherosclerosis.

Gut microbiome association with brain imaging markers, APOE genotype, calcium and vegetable intakes, and obesity in healthy aging adults.

Advanced age is a significant factor in changes to brain physiology and cognitive functions. Recent research has highlighted the critical role of the gut microbiome in modulating brain functions during aging, which can be influenced by various factors such as apolipoprotein E (APOE) genetic variance, body mass index (BMI), diabetes, and dietary intake. However, the associations between the gut microbiome and these factors, as well as brain structural, vascular, and metabolic imaging markers, have not been well explored. We recruited 30 community dwelling older adults between age 55-85 in Kentucky. We collected the medical history from the electronic health record as well as the Dietary Screener Questionnaire. We performed APOE genotyping with an oral swab, gut microbiome analysis using metagenomics sequencing, and brain structural, vascular, and metabolic imaging using MRI. Individuals with APOE e2 and APOE e4 genotypes had distinct microbiota composition, and higher level of pro-inflammatory microbiota were associated higher BMI and diabetes. In contrast, calcium- and vegetable-rich diets were associated with microbiota that produced short chain fatty acids leading to an anti-inflammatory state. We also found that important gut microbial butyrate producers were correlated with the volume of the thalamus and corpus callosum, which are regions of the brain responsible for relaying and processing information. Additionally, putative proinflammatory species were negatively correlated with GABA production, an inhibitory neurotransmitter. Furthermore, we observed that the relative abundance of bacteria from the family Eggerthellaceae, equol producers, was correlated with white matter integrity in tracts connecting the brain regions related to language, memory, and learning. These findings highlight the importance of gut microbiome association with brain health in aging population and could have important implications aimed at optimizing healthy brain aging through precision prebiotic, probiotic or dietary interventions.

A potent luminogen with NIR-IIb excitable AIE features for ultradeep brain vascular and hemodynamic three-photon imaging

Three-photon excited fluorescence microscopy (3PEFM) has emerged as a promising protocol for visualizing deep-brain vasculature and hemodynamics. However, the current situation is still far from satisfactory, due to small excitation action cross-section and short excitation wavelength of those previously reported 3PEFM luminogens. Herein, we manipulated molecular engineering by subtly regulating structural planarization/twisting to achieve ingenious integration of large three-photon absorption cross-section, high fluorescence quantum yield, ultralong near-infrared IIb excitation, and aggregation-induced emission features. The resulting molecule, namely DPCZ-BT, exhibited as high as 50.6% of fluorescence quantum yield and as large as 2.0 × 10−81 cm6s2/photon2 of three-photon absorption cross-section, which can be excited by 1665 nm fs laser and presents a recorded penetration depth of 1860 μm for deep-brain vascular structural imaging with high spatiotemporal resolution and signal-to-background ratio. Moreover, DPCZ-BT having good photostability and excellent biocompatibility is capable of impressively approaching 1600 μm depth in monitoring red blood cells flow velocity with extraordinary clarity for hemodynamics.

Definitive Diagnostic Evaluation of the Child With Arterial Ischemic Stroke and Approaches to Secondary Stroke Prevention.

In children with arterial ischemic stroke (AIS), the definitive diagnosis of stroke subtype and confirmation of stroke etiology is necessary to mitigate stroke morbidity and prevent recurrent stroke. The common causes of AIS in children are sharply differentiated from the common causes of adult AIS. A comprehensive, structured diagnostic approach will identify the etiology of stroke in most children. Adequate diagnostic evaluation relies on advanced brain imaging and vascular imaging studies. A variety of medical and surgical secondary stroke prevention strategies directed at the underlying cause of stroke are available. This review aims to outline strategies for definitive diagnosis and secondary stroke prevention in children with AIS, emphasizing the critical role of neuroimaging.

Abstract P298: Redundant Imaging in TIA: Evidence From the Nationwide Emergency Department Sample (NEDS)

Introduction: Multiple societal guidelines recommend patients with TIA be emergently imaged with brain-MRI and neurovascular screening-CTA, MRA or carotid ultrasound-to identify and treat risk factors for future stroke. Increased ED compliance with TIA imaging guidelines has previously been demonstrated, along with a substantial increase in imaging utilization over the past decade. The purpose of this study was to quantify prevalence of redundant imaging during ED work-up of TIA, and to identify imaging practices that could be targeted to reduce unnecessary expenditures. Methods: Utilizing the 2006-2017 Nationwide Emergency Department Sample, patients discharged with TIA from EDs in the US were identified using ICD-9/10 codes. Brain and neurovascular imaging obtained during the encounter was identified using CPT codes. Demographics, payor, patient income, and hospital characteristics were incorporated into a hierarchical multivariable logistic regression analysis to identify significant associations with redundant neuroimaging. Results: In 2017 there were 184,870 patients discharged from EDs with TIA. Redundant brain, brain vascular, and cervical vascular imaging was identified in 55,513(30%), 5,149(2.8%) and 1,325(0.7%) of encounters respectively. Decreased odds of obtaining redundant neuroimaging in a TIA encounter was observed in Medicaid patients(OR:0.72, 95%CI:0.64-0.81), non-trauma centers(OR:0.49, 95%CI:0.26-0.93), rural hospital locations(OR:0.18, 95%CI:0.11-0.29) and weekend encounters(OR:0.9, 95%CI:0.85-0.96). Trend analysis from 2006 to 2017 demonstrated a rise in redundant brain and neurovascular imaging from 2.3% and 0.2% of encounters respectively in 2006 to 30% and 3.5% of encounters in 2017. Using Medicare fee estimates, in 2017 redundant brain and neurovascular imaging for patients discharged from EDs with TIA resulted in additional charges of approximately 8,670,832 USD. Conclusion: Increasing utilization of imaging for workup of TIA across EDs in the US is also associated with substantial and increasing use of redundant imaging. We identify redundant brain and neurovascular imaging as areas that could be targeted to mitigate rising imaging expenditures.

Binary Organic Nanoparticles with Bright Aggregation-Induced Emission for Three-Photon Brain Vascular Imaging

Fluorogens with aggregation-induced emission (AIEgens) are promising optical agents for cellular and vascular imaging. AIEgens with bright emission in the far-red and near-infrared (NIR) region is ...

Monogenetic Stroke Syndromes in Children and Young Adults.

OBJECTIVE. The purpose of this article is to review the characteristic CT and MRI findings associated with monogenetic causes of ischemic and hemorrhagic stroke in children and young adults. CONCLUSION. Ischemic and hemorrhagic stroke in children and young adults remains a common cause of acquired disability but is underrecognized. Brain parenchymal and vascular imaging is commonly performed as part of the comprehensive evaluation of young patients presenting with stroke. Familiarity with these patterns of disease enables early recognition of an underlying inherited condition.

Facile Synthesis of Efficient Luminogens with AIE Features for Three-Photon Fluorescence Imaging of the Brain through the Intact Skull.

Visualization of the brain in its native environment is important for understanding common brain diseases. Herein, bright luminogens with remarkable aggregation-induced emission (AIE) characteristics and high quantum yields of up to 42.6% in the solid state are synthesized through facile reaction routes. The synthesized molecule, namely BTF, shows ultrabright far-red/near-infrared emission and can be fabricated into AIE dots by a simple nanoprecipitation procedure. Due to their high brightness, large Stokes shift, good biocompatibility, satisfactory photostability, and large three-photon absorption cross section, the AIE dots can be utilized as efficient fluorescent nanoprobes for in vivo brain vascular imaging through the intact skull by a three-photon fluorescence microscopy imaging technique. This is the first example of using AIE dots for the visualization of the cerebral stroke process through the intact skull of a mouse with high penetration depth and good image contrast. Such good results are anticipated to open up a new venue in the development of efficient emitters with strong nonlinear optical effects for noninvasive bioimaging of living brain.

Efficient red luminogen with aggregation-induced emission for in vivo three-photon brain vascular imaging

DCPE-TPA exhibits three morphologies with high quantum yields and nanoparticles of DCPE-TPA are utilized for in vivo 3PF imaging, achieving a penetration depth of 300 μm with a high resolution of 1.8 μm and a high signal-to-background ratio of 14.

Pulsed Laser Diode-Based Desktop Photoacoustic Tomography for Monitoring Wash-In and Wash-Out of Dye in Rat Cortical Vasculature.

Photoacoustic (PA) tomography (PAT) imaging is an emerging biomedical imaging modality useful in various preclinical and clinical applications. Custom-made circular ring array-based transducers and conventional bulky Nd:YAG/OPO lasers inhibit translation of the PAT system to clinics. Ultra-compact pulsed laser diodes (PLDs) are currently being used as an alternative source of near-infrared excitation for PA imaging. High-speed dynamic in vivo imaging has been demonstrated using a compact PLD-based desktop PAT system (PLD-PAT). A visualized experimental protocol using the desktop PLD-PAT system is provided in this work for dynamic in vivo brain imaging. The protocol describes the desktop PLD-PAT system configuration, preparation of animal for brain vascular imaging, and procedure for dynamic visualization of indocyanine green (ICG) dye uptake and clearance process in rat cortical vasculature.

Vascular Imaging Based Subtyping of Ischemic Stroke in BSMMU

Background: Most strokes and stroke related death &amp; disability happened in low and middle income countries. The clinician should be familiar with the sub typing of ischemic stroke patients and the risk factors analysis. Vascular imaging is necessary for classifying the patient. The main objective of this study was to evaluate the subtype of ischemic stroke patients and risk factor analysis of different etiology.&#x0D; Method: This is a hospital based prospective study in Bangladesh. Within the time frame of 2014 March to 2017 November; we analyzed 1978 patients of ischemic stroke within 10 days of symptom onset. Among them 877 patients have been selected for this study to whom brain imaging (CT/ MRI), vascular imaging (MRA, DSA), ECG and echocardiography have been done. We did subtyping according to TOAST criteria.&#x0D; Results: The mean age of patients was 60.5±11 years with 70.47% subjects male and 29.53% female. Within the classification of TOAST, we have found 43.87% of patients were in large artery atherosclerosis group, 23.83.% in small vessel occlusion group, 8.46% in cardiac embolism group, 19.30% in undetermined etiology group and 4.54% in other determined etiology. Among risk factors hypertension in 58.15%, DM was found in 38.42%, hypercholesterolemia in 38.88% of patients. Hypertension was significantly high in large artery atherosclerosis group.&#x0D; Conclusion: In ischemic stroke patients, large artery atherosclerosis was the most common subtype and hypertension was significant in this group.&#x0D; Bangladesh Journal of Neuroscience 2019; Vol. 35 (1): 27-32

Non-Invasive Optical Guided Tumor Metastasis/Vessel Imaging by Using Lanthanide Nanoprobe with Enhanced Down-Shifting Emission beyond 1500 nm.

Visualization of tumor vessels/metastasis and cerebrovascular architecture is vitally important for analyzing pathological states of brain diseases and a tumor's abnormal blood vessels to improve cancer diagnoses. In vivo fluorescence imaging using second near-infrared emission beyond 1500 nm (NIR-IIb) has emerged as a next generation optical imaging method with significant improvement in imaging sensitivity and spatial resolution. Unfortunately, a highly biocompatible probe capable of generating NIR-IIb emission with sufficient brightness and uniformed size is still scarce. Here, we have proposed the poly(acrylic acid) (PAA)-modified NaLnF4:40Gd/20Yb/2Er nanorods (Ln = Y, Yb, Lu, PAA-Ln-NRs) with enhanced downshifting NIR-IIb emission, high quantum yield (QY), relatively narrow bandwidth (∼160 nm), and high biocompatibility via Ce3+ doping for high performance NIR-IIb bioimaging. The downshifting emission beyond 1500 nm is improved by 1.75-2.2 times with simultaneously suppressing the upconversion (UC) path in Y, Yb, and Lu hosts via Ce3+ doping. Moreover, compared with the traditionally used Y-based host, the QY of NIR-IIb emission in the Lu-based probe in water is improved from 2.2% to 3.6%. The explored bright NIR-IIb emitted PAA-Lu-NRs were used for high sensitivity small tumor (∼4 mm)/metastatic tiny tumor detection (∼3 mm), tumor vessel visualization with high spatial resolution (41 μm), and brain vessel imaging. Therefore, our findings open up the opportunity of utilizing the lanthanide based NIR-IIb probe with bright 1525 nm emission for in vivo optical-guided tumor vessel/metastasis and noninvasive brain vascular imaging.

Whole brain vascular imaging in a mouse model of Alzheimer’s disease with two-photon microscopy

Given known correlations between vascular health and cognitive impairment, the development of tools to image microvasculature in the whole brain could help investigate these correlations. We explore the feasibility of using an automated serial two-photon microscope to image fluorescent gelatin-filled whole rodent brains in three-dimensions (3-D) with the goal of carrying group studies. Vascular density (VD) was computed using automatic segmentation combined with coregistration techniques to build a group-level vascular metric in the whole brain. Focusing on the medial prefrontal cortex, cerebral cortex, the olfactory bulb, and the hippocampal formation, we compared the VD of three age groups (2-, 4.5-, and 8-months-old), for both wild type mice and a transgenic model (APP/PS1) with pathology resembling Alzheimer's disease (AD). We report a general loss of VD caused by the aging process with a small VD increase in the diseased animals in the somatomotor and somatosensory cortical regions and the olfactory bulb, partly supported by MRI perfusion data. This study supports previous observations that AD transgenic mice show a higher VD in specific regions compared with WT mice during the early and late stages of the disease (4.5 to 8 months), extending results to whole brain mapping.

Non-invasive through-skull brain vascular imaging and small tumor diagnosis based on NIR-II emissive lanthanide nanoprobes beyond 1500 nm

Optical bioimaging by using the new short-wavelength infrared window (SWIR, also named as NIR-II, 1000–1700 nm) is emerged as a next generation imaging technique for disease diagnosis owing to the unprecedented improvements in imaging sensitivity and spatial resolution. However, it is challenging to search new imaging agents with highly biocompatible and bright narrow-band emission located in the 1500–1700 nm (referred as NIR-IIb) region. Here we developed high quality polyacrylic acid (PAA) modified NaYF4:Gd/Yb/Er nanorods (PAA-NRs) with remarkably enhanced NIR-IIb emission and decent bio-compatibility for in vivo cerebral vascular bioimaging and small tumor visualization. These PAA-NRs present efficient narrow-band NIR-IIb emission centered at 1520 with 182 nm of band-width. Owing to the highly efficient NIR-IIb emission, NIR-IIb imaging-guided small tumor (4 mm in diameter) detection is achieved. More importantly, non-invasive optical brain vessel bioimaging with high spatial (∼43.65 μm) and temporal resolution through scalp and skull is obtained without craniotomy. These findings open up the opportunity of designing non-invasive approach for visualization the brain vasculature and tumor in biomedical application.

Microbubble Localization for Three-Dimensional Superresolution Ultrasound Imaging Using Curve Fitting and Deconvolution Methods.

Superresolution algorithms in ultrasound imaging are attracting the interest of researchers recently due to the ability of these methods to enable enhanced vascular imaging. In this study, two superresolution imaging methods are compared for postprocessing images of microbubbles generated using passive acoustic mapping (PAM) methods with a potential application of three-dimensional (3-D) brain vascular imaging. The first method is based on fitting single bubble images one at a time with a 3-D Gaussian profile to localize the microbubbles and a superresolution image is then formed using the uncertainty of the localization as the standard deviation of the Gaussian profile. The second superresolution method is based on image deconvolution that processes multiframe resolution-limited images iteratively and estimates the intensity at each pixel of the superresolution image without the need for localizing each microbubble. The point spread function is approximated by a Gaussian curve which is similar to the beam response of the hemispherical transducer array used in our experimental setup. The Cramér-Rao Bounds of the two estimation techniques are derived analytically and the performance of these techniques is compared through numerical simulations based on experimental PAM images. For linear and sinusoidal traces, the localization errors between the estimated peaks by the fitting-based method and the actual source locations were 220 10m and 210 5m, respectively, as compared to 74 10 m and 59 8 m with the deconvolution-based method. However, in terms of the running time and the computational costs, the curve fitting technique outperforms the deconvolution-based approach.

Implementation of a Rapid, Protocol-based TIA Management Pathway.

IntroductionOur goal was to assess whether use of a standardized clinical protocol improves efficiency for patients who present to the emergency department (ED) with symptoms of transient ischemic attack (TIA).MethodsWe performed a structured, retrospective, cohort study at a large, urban, tertiary care academic center. In July 2012 this hospital implemented a standardized protocol for patients with suspected TIA. The protocol selected high-risk patients for admission and low/intermediate-risk patients to an ED observation unit for workup. Recommended workup included brain imaging, vascular imaging, cardiac monitoring, and observation. Patients were included if clinical providers determined the need for workup for TIA. We included consecutive patients presenting during a six-month period prior to protocol implementation, and those presenting between 6–12 months after implementation. Outcomes included ED length of stay (LOS), hospital LOS, use of neuroimaging, and 90-day risk of stroke or TIA.ResultsFrom 01/2012 to 06/2012, 130 patients were evaluated for TIA symptoms in the ED, and from 01/2013 to 06/2013, 150 patients. The final diagnosis was TIA or stroke in 45% before vs. 41% after (p=0.18). Following the intervention, the inpatient admission rate decreased from 62% to 24% (p<0.001), median ED LOS decreased by 1.2 hours (5.7 to 4.9 hours, p=0.027), and median total hospital LOS from 29.4 hours to 23.1 hours (p=0.019). The proportion of patients receiving head computed tomography (CT) went from 68% to 58% (p=0.087); brain magnetic resonance (MR) imaging from 83% to 88%, (p=0.44) neck CT angiography from 32% to 22% (p=0.039); and neck MR angiography from 61% to 72% (p=0.046). Ninety-day stroke or recurrent TIA among those with final diagnosis of TIA was 3% for both periods.ConclusionImplementation of a TIA protocol significantly reduced ED LOS and total hospital LOS.

Molecular Engineering of Photoacoustic Performance by Chalcogenide Variation in Conjugated Polymer Nanoparticles for Brain Vascular Imaging.

As conjugated polymer nanoparticles (CPNs) have attracted growing interest as photoacoustic (PA) imaging contrast agents, revelation of the relationship between the molecular structure of conjugated polymers and PA property is highly in demand. Here, three donor-acceptor-structured conjugated polymer analogs are designed, where only a single heteroatom of acceptor units changes from oxygen to sulfur to selenium, allowing for systematic investigation of the molecular structure-PA property relationship. The absorption and PA spectra of these CPNs can be facilely tuned by changing the heteroatoms of the acceptor units. Moreover, the absorption coefficient, and in turn the PA signal intensity, decreases when the heteroatom changes from oxygen to sulfur to selenium. As these CPNs exhibit weak fluorescence and similar photothermal conversion efficiency (≈70%), their PA intensities are approximately proportional to their absorption coefficients. The in vivo brain vasculature imaging in this study also demonstrates this trend. This study provides a simple but efficient strategy to manipulate the PA properties of CPNs through changing the heteroatom at key positions.

Transient Monocular Vision Loss on Awakening: A Benign Amaurotic Phenomenon.

Transient monocular vision loss (TMVL) is an alarming symptom owing to potentially serious etiologies such as thromboembolism or giant cell arteritis. Our objective is to describe the phenomenon of TMVL present on awakening, which may represent a distinct and benign entity. We performed a retrospective observational case series of 29 patients who experienced TMVL on awakening. Patients who described monocular dimming or blackout of vision were included, and those with blurred vision, concurrent eye pain, and binocular vision loss were excluded. Descriptive statistics were used to summarize the study population. Of the 29 patients we studied, 90% (n = 26) were female and 48% had crowded discs (cup-to-disc ratio ≤0.2). The mean age was 45.4 years, although women were significantly younger than men (mean ages 43.4 and 62.7 years, respectively, P = 0.017). Brain magnetic resonance imaging and vascular imaging (magnetic resonance angiography, computed tomographic angiography, or carotid Doppler) were performed in 69% and 55% of cases, respectively, and were uniformly negative. In 14 patients for whom clear follow-up data could be obtained, no medically or visually significant sequelae of this syndrome were found, and 50% experienced resolution of symptoms. Evaluation was uniformly negative when patients described waking with isolated vision loss in 1 eye with subsequent resolution, usually in less than 15 minutes. The natural history seems benign with symptoms frequently remitting spontaneously. This visual phenomenon may represent an autoregulatory failure resulting in a supply/demand mismatch during low-light conditions.