Clinical features and imaging markers of small vessel disease in symptomatic acute subcortical cerebral microinfarcts

BACKGROUND: As currently defined, recent small subcortical infarcts (RSSI) do not have a lower size boundary, and the smallest diffusion-weighted imaging (DWI) infarcts, which we term acute subcortical cerebral microinfarcts (As-CMI) with lesion diameter less than 5 mm, might have clinical implications distinct from RSSI. We aimed to investigate the distinct characteristics of As-CMI as compared to the larger size of RSSI regarding vascular risk factors, clinical manifestation, radiological markers of SVD distribution, and outcomes. METHODS: In a consecutive cohort, patients were selected with a magnetic resonance DWI-confirmed RSSI between January 2010 and November 2020. We measured axial infarct diameter and classified patients into two groups: The As-CMI group (diameter < 5 mm) versus the Larger RSSI group (diameter 5-20 mm). Clinical variables, including vascular risk factors, clinical symptoms/signs, lesion locations, and radiological markers of cerebral small vessel disease (SVD) on MRI were analyzed between the two groups. Patients were followed up for 12 months and functional outcomes were measured by the modified ranking scale (mRS). RESULTS: In a total of 584 patients with RSSI, 23 (3.9%) were defined as As-CMI. The most common neurological deficits with As-CMI were hemiparalysis (n = 20), followed by central facial/lingual palsy (n = 10) and hemidysesthesia (n = 10). Most As-CMIs were located in the basal ganglia (n = 11), followed by the thalamus (n = 5) and centrum semiovale (n = 4). No different regional distributions and symptoms/signs frequencies were found between the two groups except for a lower percentage of dysarthria in the As-CMI group (p = 0.008). In a multivariate analysis, patients with As-CMI were independently associated with the presence of lacunes (adjusted odds ratio [aOR] 2.88; 95% confidence interval [CI] 1.21–6.84), multiple lacunes (aOR 3.5, CI 1.29–9.48) and higher total SVD burden (aOR 1.68, CI 1.11–2.53). Patients with As-CMI did not show a better functional outcome after 12 months of follow-up. CONCLUSIONS: Patients with As-CMI had a non-specific clinical profile but a higher burden of SVD, indicating As-CMI might be s sign of more severe small vascular injury. Whether its vascular features are associated with worse cognitive outcomes requires further investigation

Retinal ganglion cell-inner plexiform layer, white matter hyperintensities, and their interaction with cognition in older adults

PurposeWe explored the interaction of optical coherence tomography (OCT) parameters and white matter hyperintensities with cognitive measures in our older adult cohort.MethodsThis observational study enrolled participants who underwent a comprehensive neuropsychological battery, structural 3-T brain magnetic resonance imaging (MRI), visual acuity examination, and OCT imaging. Cerebral small vessel disease (CSVD) markers were read on MR images; lacune, cerebral microbleeds (CMB), white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS), were defined according to the STRIVE standards. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses (μm) were measured on the OCT tool.ResultsOlder adults with cognitive impairment (CI) showed lower RNFL (p = 0.001), GCIPL (p = 0.009) thicknesses, and lower hippocampal volume (p = 0.004) when compared to non-cognitively impaired (NCI). RNFL (p = 0.006) and GCIPL thicknesses (p = 0.032) correlated with MoCA scores. GCIPL thickness (p = 0.037), total WMH (p = 0.003), PWMH (p = 0.041), and DWMH (p = 0.001) correlated with hippocampal volume in our older adults after adjusting for covariates. With hippocampal volume as the outcome, a significant interaction (p &lt; 0.05) between GCIPL and PWMH and total WMH was observed in our older adults.ConclusionBoth GCIPL thinning and higher WMH burden (especially PWMH) are associated with hippocampal volume and older adults with both pathologies are more susceptible to subclinical cognitive decline

Automated evaluation of retinal hyperreflective foci changes in diabetic macular edema patients before and after intravitreal injection

PurposeFast and automated reconstruction of retinal hyperreflective foci (HRF) is of great importance for many eye-related disease understanding. In this paper, we introduced a new automated framework, driven by recent advances in deep learning to automatically extract 12 three-dimensional parameters from the segmented hyperreflective foci in optical coherence tomography (OCT).MethodsUnlike traditional convolutional neural networks, which struggle with long-range feature correlations, we introduce a spatial and channel attention module within the bottleneck layer, integrated into the nnU-Net architecture. Spatial Attention Block aggregates features across spatial locations to capture related features, while Channel Attention Block heightens channel feature contrasts. The proposed model was trained and tested on 162 retinal OCT volumes of patients with diabetic macular edema (DME), yielding robust segmentation outcomes. We further investigate HRF’s potential as a biomarker of DME.ResultsResults unveil notable discrepancies in the amount and volume of HRF subtypes. In the whole retinal layer (WR), the mean distance from HRF to the retinal pigmented epithelium was significantly reduced after treatment. In WR, the improvement in central macular thickness resulting from intravitreal injection treatment was positively correlated with the mean distance from HRF subtypes to the fovea.ConclusionOur study demonstrates the applicability of OCT for automated quantification of retinal HRF in DME patients, offering an objective, quantitative approach for clinical and research applications

Microvascular Changes in the Retina Correlate with MRI Markers in Patients with Early-Onset Dementia

Background and Aims: Recent reports suggest that results from imaging retinal microvascular changes with optical coherence tomography angiography (OCTA) in dementia patients reflect cerebral microcirculation changes that occur during dementia. Macula microvascular impairment has been shown in dementia patients compared to controls, but very little is known about its correlation with radiological visual rating scores associated with dementia. We aimed to explore the association between retinal microvasculature and radiological visual rating in early-onset dementia (EOD) patients. Methods: Swept-source OCTA (SS-OCTA) was used to image the retinal microvasculature of all EOD patients. Automated software in the OCTA tool segmented and measured the densities in the superficial vascular plexus (SVC) and deep vascular plexus (DVC) and foveal avascular zone (FAZ) areas. Radiological visual rating scores were evaluated on all MR images. Results: Medial temporal lobe atrophy (MTA) scores significantly correlated with FAZ area (p = 0.031) in EOD patients after adjusting for risk factors. PWMH correlated with SVC (p = 0.032) while DWMH significantly correlated with SVC (p = 0.007), DVC (p = 0.018) and FAZ (p = 0.001) in EOD patients. Discussion: FAZ changes correlated with MTA scores in EOD patients, while retinal microvasculature correlated with white matter hyperintensity. Our report suggests that microvascular changes in the retina may reflect cortical changes in the brain of EOD patients

Retinal Microvascular Impairment in the Early Stages of Parkinson's Disease

To detect the retinal microvascular impairment using optical coherence tomography angiography (OCT-A) in patients with Parkinson's disease (PD) and find a correlation between the microvascular impairment and the neuronal damage. This is a prospective, observational study including 49 eyes from 38 PD patients in their early stages and 34 eyes from 28 healthy controls with comparable age range. Macula microvasculature was evaluated with the spectral-domain optical coherence tomography (SD-OCT) angiography and intraretinal layer thickness evaluated with the SD-OCT. A custom algorithm was used for custom segmentation of retinal thickness and quantification of the superficial and deep microvascular density of the macula, respectively. PD patients showed reduced microvascular density in most of the areas of the whole retina. In the superficial retinal capillary plexus, statistical difference (P < 0.01) was seen in the total annular zone (TAZ), superior, temporal, inferior, and nasal zones. In PD patients, there was a strong correlation between the average ganglion cell layer and inner plexiform (GCIP) thickness and the TAZ of the superficial microvascular density (r = 0.062, P = 0.032). We demonstrated that retinal microvascular density decreased in PD patients. The correlation between microvascular impairment in the superficial retinal capillary layer and GCIP thinning also revealed that the retinal microvascular abnormality may contribute to the neurodegeneration in PD patients. OCT-A with quantitative analysis offers a new path of study and will likely be useful in the future as an objective biomarker for detecting vessel impairment in early stages of PD

Characterization of Macular Structural and Microvascular Changes in Thalamic Infarction Patients: A Swept-Source Optical Coherence Tomography&ndash;Angiography Study

Background: The retina and brain share similar neuronal and microvascular features. We aimed to investigate the retinal thickness and microvasculature in patients with thalamic infarcts compared with control participants. Material and methods: Swept-source optical coherence tomography (SS-OCT) was used to image the macular thickness (retinal nerve fiber layer, RNFL; ganglion cell-inner plexiform layer, GCIP), while OCT angiography was used to image the microvasculature (superficial vascular plexus, SVP; intermediate capillary plexus, ICP; deep capillary plexus, DCP). Inbuilt software was used to measure the macular thickness (&micro;m) and microvascular density (%). Lesion volumes were quantitively assessed based on structural magnetic resonance images. Results: A total of 35 patients with unilateral thalamic infarction and 31 age&ndash;sex-matched controls were enrolled. Compared with control participants, thalamic infarction patients showed a significantly thinner thickness of RNFL (p &lt; 0.01) and GCIP (p = 0.02), and a lower density of SVP (p = 0.001) and ICP (p = 0.022). In the group of patients, ipsilateral eyes showed significant reductions in SVP (p = 0.033), RNFL (p = 0.01) and GCIP (p = 0.043). When divided into three groups based on disease duration (&lt;1 month, 1&ndash;6 months, and &gt;6 months), no significant differences were found among these groups. After adjusting for confounders, SVP, ICP, DCP, RNFL, and GCIP were significantly correlated with lesion volume in patients. Conclusions: Thalamic infarction patients showed significant macular structure and microvasculature changes. Lesion size was significantly correlated with these alterations. These findings may be useful for further research into the clinical utility of retinal imaging in stroke patients, especially those with damage to the visual pathway

Data_Sheet_1_Relationships between cerebral small vessel diseases markers and cognitive performance in stroke-free patients with atrial fibrillation.docx

BackgroundAtrial fibrillation (AF) is related to an increased risk of cognitive dysfunction. Besides clinically overt stroke, AF can damage the brain via several pathophysiological mechanisms. We aimed to assess the potential mediating role of cerebral small vessel disease (SVD) and cognitive performance in individuals with AF.MethodsStroke-free individuals with AF from the cardiological outpatient clinic at West China Hospital of Sichuan University were recruited. Extensive neuropsychological testing tools were assessed including global function, domains of attention, executive functions, learning, and memory. 3 T magnetic resonance imaging (MRI) was used for SVD markers assessment of white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS). The correlation between SVD markers and cognitive measures was analyzed by multivariate linear regression models.ResultsWe finally enrolled 158 participants, of whom 95 (60.1%) were males. In multivariate models, the presence of lacunes independently associated with Montreal Cognitive Assessment (Model 1: ß = 0.52, Model 2: ß = 0.55), Rey Auditory Verbal Learning Test-immediate and delayed recall (Model 1: ß = 0.49; ß = 0.69; Model 2: ß = 0.53; ß = 0.73) as well as Stroop-Acorrect (Model 1: ß = 0.12; Model 2: ß = 0.13), while total WMH severity independently associated with Strooptime-A (Model 1: ß = 0.24; Model 3: ß = 0.27), Strooptime-B (Model 1: ß = 0.17; Model 3: ß = 0.17), Strooptime-C (Model 1: ß = 0.22; Model 3: ß = 0.21) and Shape Trail Test-A (Model 1: ß = 0.17; Model 3: ß = 0.16).ConclusionIn our cohort of stroke-free individuals with AF, lacunes, and WMHs were independently associated with cognitive decline while EPVS and CMBs did not show significance. Assessment of SVD MRI markers might be valuable for cognition risk stratification and facilitate optimal management of patients with AF.</p

DataSheet_1_Retinal structural and microvascular changes in myelin oligodendrocyte glycoprotein antibody disease and neuromyelitis optica spectrum disorder: An OCT/OCTA study.docx

PurposeTo compare the optical coherence tomography (OCT)/OCT angiography (OCTA) measures in patients with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD).MethodsTwenty-one MOG, 21 NMOSD, and 22 controls were enrolled in our study. The retinal structure [retinal nerve fiber layer (RNFL) and ganglion cell–inner plexiform layer (GCIPL)] was imaged and assessed with the OCT; OCTA was used to image the macula microvasculature [superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP)]. Clinical information such as disease duration, visual acuity, and frequency of optic neuritis and disability was recorded for all patients.ResultsCompared with NMOSD patients, MOGAD patients showed significantly reduced SVP density (P = 0.023). No significant difference (P > 0.05) was seen in the microvasculature and structure when NMOSD-ON was compared with MOG-ON. In NMOSD patients, EDSS, disease duration, reduced visual acuity, and frequency of ON significantly correlated (P ConclusionsDistinct structural and microvascular changes were identified in MOGAD patients compared with NMOSD patients suggesting that the pathological mechanisms are different in NMOSD and MOGAD. Retinal imaging via the SS-OCT/OCTA might have the potential to be used as a clinical tool to evaluate the clinical features associated with NMOSD and MOGAD.</p