This work was supported by matching and donation funds (Cerebrovascular Research Fund, SHAC Matching Grant, UGC Matching Grant, and Dr. William Mong Research Fund in Neurology awarded to Professor R.T.F. Cheung).

The study protocol was approved by the Institutional Review Board of the University of Hong Kong / Hospital Authority Hong Kong West Cluster (HKU/HA HKW IRB) for human research.
1. Participants
<ol>
	<li>Recruit otherwise healthy elderly Chinese subjects (from 65 to 99 years old, mean age 72) with a history of hypertension for at least 5 years.</li>
	<li>Exclude participants with any disease affecting the cognitive function and/or with any disability hindering the completion of the required assessment, including but not limited to stroke, dementia, encephalitis, depression, diabetes mellitus and coronary heart diseases.</li>
	<li>Inform the participant of the scope of the study before obtaining the written consent.</li>
</ol>
2. Neuropsychological assessment
<ol>
	<li>Arrange an interview for each participant to administer a battery of neuropsychological tests focusing on six cognitive domains (Table 1) and to collect the demographic and clinical data. Review the participant&#39;s medical records to ensure the reliability of relevant information.</li>
	<li>Forward/Backward digit span tests
	<ol>
		<li>Prepare groups of random digit sequences of increasing length (Figure 1A). Start with a three-digit sequence. Read out the digit sequence aloud at a rate of one digit per second. Ask the participant to immediately recall the digit sequence verbally in the Forward digit span test10.</li>
		<li>Have the participant recall progressively longer digit sequences with one more digit each time the participant has successfully recalled the digit sequence without any error.</li>
		<li>Give a different digit sequence of the same length if the participant has failed in the first trial of a specific length. End the test if the participant has failed again. Discontinue the test also when the participant has failed up to three times in total.</li>
		<li>Record the longest length of the digit sequence the participant has successfully recalled without any error.</li>
		<li>Start with a three-digit sequence and ask the participant to recall the digit sequence in a reverse order in the Backward digit span test. Follow the steps of Forward digit span test otherwise.</li>
	</ol>
	</li>
	<li>MoCA
	<ol>
		<li>Administer MoCA using the validated version. Use the Cantonese version to measure global cognitive function in our protocol and to construct compound domain scores11,12.</li>
		<li>MoCA verbal learning task: Read five words from different categories (<img align="center" alt="Equation" src="/files/ftp_upload/61017/61017char1.jpg" /> as Chinese characters for face, cloth, church, daisy and red color in our protocol, respectively) to the participant. Ask the participant to immediately recall the words. Repeat the reading and immediate recall a second time. Remind the participant about a delayed recall 5 minutes later. Assign one point to each correct word during the delayed recall.</li>
		<li>MoCA naming task: Show pictures of three animals (lion, rhinoceros and camel in our protocol) and ask the participant to tell their names. Assign one point to each correct name.</li>
		<li>MoCA repetition task: Read a simple sentence to the participant and ask the participant to immediately repeat it. Repeat the procedure with a more complex sentence. Assign one point to each correct repetition.</li>
		<li>MoCA drawing a cube task: Ask the participant to copy a cube printed on a sheet of paper in nearby blank space. Assign one point if the cube is copied correctly.</li>
		<li>MoCA drawing a clock task: Ask the participant to draw a clock face with time at 11:10. Assign one point each for accurate completion of the clock face, numbers and pointers, respectively.</li>
	</ol>
	</li>
	<li>Stroop test
	<ol>
		<li>Use the Chinese Translated Victoria Version of the Stroop test in our protocol13.</li>
		<li>Inform the participant to finish three sessions each with 24 stimuli printed in four different colors in 6 rows within a sheet of paper (Figure 1B). Start with dots (color naming subtask), next with four Chinese characters (of meaning not related to any color; neutral color subtask), and finally with four Chinese characters (of meaning related to a color but in another color different from their meaning, e.g., <img align="center" alt="Equation" src="/files/ftp_upload/61017/61017char2.jpg" /> as a Chinese character for &#34;red&#34; printed in green; interference subtask). Remind the participant to name the color of the printed stimuli (i.e., green, blue, yellow or red) and disregard their meaning.</li>
		<li>Allow the participant to use the first 4 stimuli in each session as a practice to ensure a full understanding of the rules. Point out any error during the practice stage and encourage the participant to correctly name the color.</li>
		<li>Remind and encourage the participant to complete the remaining 20 stimuli as quickly and accurately as possible. Record the time used by the participant to complete each session (excluding the practice stage).</li>
	</ol>
	</li>
	<li>SDMT
	<ol>
		<li>Pair 1 to 9 digits in the numeric order with nine unassociated symbols14.</li>
		<li>Print a list of the nine symbols in a random order without the corresponding digits (Figure 1C). Ask the participant to fill in the blank with the correctly paired digit below each symbol. Allow the participant to check back and forth the printed pairs for reference at any time of the test.</li>
		<li>Allow the participant to try filling the first 10 blanks as a practice to ensure a full understanding of the rules. Point out any error during the practice stage and encourage the participant to be correct.</li>
		<li>Remind and encourage the participant to fill in the blank as quickly and accurately as possible in the next 90 seconds. Record the number of correct responses in the written-SDMT.</li>
		<li>Continue the test but ask the participant to provide the correctly paired digit verbally. Record the number of correct responses in the oral-SDMT.</li>
	</ol>
	</li>
	<li>Verbal fluency
	<ol>
		<li>Ask the participant to provide a verbal list of names belonged to each of the three categories (i.e., animals, vegetables and fruits) separately in one minute for each category15.</li>
		<li>Record the total number of names for each category.</li>
	</ol>
	</li>
</ol>
3. MRI acquisition and Visual rating of SCLs on MRI
<ol>
	<li>Perform a multi-sequence 3-Tesla MRI scanning for the participant using the parameters and including the sequences summarized in Table 2. Complete the MRI scanning within one month of the neuropsychological assessment.</li>
	<li>Identify and visually rate SCLs on MRI according to standard criteria by experienced raters in an anonymous manner. Ensure good intra- and inter-rater reliability.</li>
	<li>Use T1-weighted and fluid-attenuated inversion recovery (FLAIR) images to identify SLs (as hypointense foci of 2-15 mm diameter on both sequences, usually with a hyperintence rim on FLAIR images) and their locations (Figure 2A). Re-confirm the SLs on T2-weighted images (as hyperintense foci at the same locations).
	<ol>
		<li>Search all brain regions in a pre-specified order from anterior to posterior and from one side to the other to avoid any omission (i.e., starting from frontal lobe, island lobe, basal ganglion, thalamus, temporal lobe, parietal lobe, occipital lobe, cerebellum and finally to brain stem, and starting from the left side and then to the right side).</li>
	</ol>
	</li>
	<li>Use susceptibility-weighted imaging (SWI) to identify CMBs (as punctuate or small round/oval hypointense foci of 2-10 mm diameter) and their locations (Figure 2B). Divide the whole brain region into 7 anatomical locations (i.e., cortex and grey-white junction, subcortical white matter, basal ganglia grey matter, internal and external capsule, thalamus, brain stem and cerebellum) according to the Brain Observer MicroBleed Scale (BOMBS)16.</li>
	<li>Label SLs and CMBs as strictly lobar SLs and CMBs, respectively, when they are confined to the lobar white matter. Label them as deep SLs and CMBs, respectively, when deep or infratentorial lesions are observed with and without additional lobar lesions17,18.</li>
	<li>Use T2-weighted and FLAIR images to identify WMHs (bilateral, almost symmetrical hyperintense areas) (Figure 2C). Re-confirm WMHs on T1-weighted images (as isointense or hypointense areas at the same locations). Recognize PVHs and DWMHs separately. Use the Fazekas scale to rate the severity of WMHs19.</li>
	<li>Rate PVHs appearing as &#34;caps&#34; or pencil-thin lining, smooth &#34;halo&#34; and irregular signal extending into the deep white matter as grade 1, 2 and 3, respectively. Rate DWMHs appearing as punctate foci, small confluent areas and large confluent areas as grade 1, 2 and 3, respectively.</li>
</ol>
4. Statistical analysis
<ol>
	<li>Perform all analyses using the statistical package SPSS 22.0 for MacBook.</li>
	<li>Transform the participant&#39;s score for each test using z transformation: 
	<img alt="Equation" src="/files/ftp_upload/61017/61017eq1.jpg" /></li>
	<li>Invert the Stroop test scores so that a higher score represents better performance.</li>
	<li>Calculate a compound score for each cognitive domain by averaging the mean z score of all component tests under the same domain8,9: 
	The compound score for executive function = (z score of backward digit span + z score of Stroop interference + z score of verbal fluency) / 3</li>
	<li>Use linear regression models to explore the association between each type of SCLs and cognitive function, adjusting for age, sex, and educational level. Perform further analyses after adjusting for vascular risk factors if significant associations are identified.</li>
	<li>Conduct additional analyses after further adjustment for the other types of SCLs in order to assess the independence of the association between the load of a specific type of SCLs and cognition.</li>
</ol>

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K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Atrophy+of+the+left+dorsolateral+prefrontal+cortex+is+associated+with+poor+performance+in+verbal+fluency+in+elderly+poststroke+women.">Atrophy of the left dorsolateral prefrontal cortex is associated with poor performance in verbal fluency in elderly poststroke women.</a> Neural Regeneration Research. 8 (4), 346-356 (2013).</li><li>Dufouil, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Severe+cerebral+white+matter+hyperintensities+predict+severe+cognitive+decline+in+patients+with+cerebrovascular+disease+history.">Severe cerebral white matter hyperintensities predict severe cognitive decline in patients with cerebrovascular disease history.</a> Stroke. 40 (6), 2219-2221 (2009).</li><li>Mungas, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Longitudinal+volumetric+MRI+change+and+rate+of+cognitive+decline.">Longitudinal volumetric MRI change and rate of cognitive decline.</a> Neurology. 65 (4), 565-571 (2005).</li><li>Benjamin, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lacunar+Infarcts,+but+Not+Perivascular+Spaces,+Are+Predictors+of+Cognitive+Decline+in+Cerebral+Small-Vessel+Disease.">Lacunar Infarcts, but Not Perivascular Spaces, Are Predictors of Cognitive Decline in Cerebral Small-Vessel Disease.</a> Stroke. 49 (3), 586-593 (2018).</li><li>Carey, C. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Subcortical+lacunes+are+associated+with+executive+dysfunction+in+cognitively+normal+elderly.">Subcortical lacunes are associated with executive dysfunction in cognitively normal elderly.</a> Stroke. 39 (2), 397-402 (2008).</li><li>Zi, W., Duan, D., Zheng, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cognitive+impairments+associated+with+periventricular+white+matter+hyperintensities+are+mediated+by+cortical+atrophy.">Cognitive impairments associated with periventricular white matter hyperintensities are mediated by cortical atrophy.</a> Acta Neurologica Scandinavica. 130 (3), 178-187 (2014).</li><li>Vernooij, M. 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The authors have no conflict of interest to declare.

In the study, we have combined the results of a battery of neuropsychological assessment and findings of a multi-sequence MRI examination to evaluate the impact of different types of SCLs on various cognitive functions. The major types of SCLs were examined (i.e., CMBs, SLs and WMHs). As previous studies have revealed that SCLs in different locations may represent different pathology and lead to different consequences, we categorized CMBs and SLs into strictly lobar (i.e., lobar only without deep ones) and deep ones (wit...

Silent lacunes (SLs), cerebral microbleeds (CMBs) and white matter hyperintensities (WMHs) are referred to as silent cerebrovascular lesions (SCLs). Two types of WMHs are recognized: periventricular WMHs (PVHs) and deep WMHs (DWMHs). SCLs were once regarded as benign lesions without clinical significance. After decades of research, SCLs are now confirmed to be linked to varying functional impairment and cognitive deficits1,2. Nevertheless, consistent evidence is still limited in the spectrum and magnitude of cognitive effects of different types of SCLs. Moreover, the underlying mechanisms are elusive.
Most previous studies either recruited hospital patients with severe medical conditions3,4,5 or included participants with advanced cerebral small vessel diseases6,7. The heterogeneity of the participants among different studies has partly contributed to the inconsistent results. To exclude these confounding factors, we conducted the current one-centered&#160;study as an attempt to provide a clear picture through assessment of a relatively large, pure cohort recruited from a primary care setting. Furthermore, previous studies have predominantly focused on one or two types of SCLs and did not fully evaluate the independent associations between individual SCLs and specific cognitive functions. Therefore, we assessed various types of SCLs in the current study.
Neuropsychological tests are widely used to assess cognitive function of specific domains. They are useful in differentiation between normal aging and early cognitive impairment. Results of properly conducted neuropsychological assessment are sensitive in discerning behavioral and functional deficits. A battery of structured neuropsychological tests was chosen, including forward and backward digit span tests, symbol digit modalities test (SDMT), Stroop test, verbal fluency test and Montreal Cognitive Assessment (MoCA). Scores from these tests were grouped and combined to represent performance in different cognitive domains8,9. Such a method is widely used and is time efficient. A major drawback is that different neuropsychological tests may partly overlap in their tested domains. A more specific alternative is to use computer-based assessment with well-designed modules constructed using the E-Prime system, which is time-consuming and may not be suitable for screening purposes.
In conclusion, we aimed to assess the associations between the burden of different SCLs and impairment of various cognitive domains. Furthermore, vascular risk factors and other types of SCLs were controlled for to determine the distinct and independent profile&#160;of cognitive impairment of each type of SCLs.

<table><tbody><tr><td>3T MRI</td><td>Philips Medical Systems</td><td></td><td></td></tr></tbody></table>

evaluation of the cognitive performance of hypertensive patients with silent cerebrovascular lesions

Evidence accumulated from the last decade has proven that silent cerebrovascular lesions (SCLs) and their underlying pathogenic processes contribute to cognitive decline in the elderly. However, the distinct effects of each type of the lesions on cognitive performance remain unclear. Moreover, research data from Chinese elderly with SCLs is scarce. In this study, 398 otherwise healthy hypertensive elderly subjects (median age 72 years) were included and assessed. All participates were required to complete a battery of structured neuropsychological assessment, including forward and backward digit span tests, symbol digit modalities test, Stroop test, verbal fluency test and Montreal Cognitive Assessment. These tests were used to assess attention, executive function, information processing speed, language, memory and visuospatial function. A multi-sequence 3T MRI scanning was arranged within one month of the neuropsychological assessment to evaluate the burden of SCLs. SCLs were rated visually. Cerebral microbleeds (CMBs) and silent lacunes (SLs) were identified as strictly lobar CMBs and SLs or deep CMBs and SLs according to their locations, respectively. Similarly, white matter hyperintensities (WMHs) were separated into periventricular WMHs (PVHs) and deep WMHs (DWMHs). A series of linear regression models were used to assess the correlation between each type of SCLs and individual cognitive function domain. The results showed that CMBs tend to impair language-related cognition. Deep SLs affect executive function, but this association disappeared after controlling for other types of SCLs. PVHs, rather than DWMHs, are associated with cognitive decline, especially in executive function and processing speed. It is concluded that different aspects of SCLs have differential impact on cognitive performance in hypertensive elderly Chinese.

The mean age of the 398 participants was 72.0 (from 65 to 99, SD = 5.1) years, and there were 213 men (53. 5%; Table 3). Table 4 summarizes the neuropsychological assessment results. Only 5 participants had all four types of SCLs. One or more types of SCLs were found in 169 (42.5%) participants, and 35 (8.8%) and 17 (4.3%) participants had 2 and 3 types of SCLs, respectively (Table 5).
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Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions

Here, we present a protocol to assess whether various types of silent cerebrovascular lesions are differentially associated with deficits in certain cognitive domains in a cohort of 398 hypertensive elderly Chinese, using a combination of neuropsychological tests and multi-sequence 3T MRI scanning.

Evidence accumulated from the last decade has proven that silent cerebrovascular lesions (SCLs) and their underlying pathogenic processes contribute to ...

evaluation-cognitive-performance-hypertensive-patients-with-silent

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JoVE Journal

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2.9K Views.  The First Affiliated Hospital of Wenzhou Medical University. Stille cerebrovasculaire laesies kunnen verschillende functionele stoornissen en cognitieve tekorten veroorzaken. De verschillende effecten van verschillende soorten laesies op cognitieve prestaties blijven echter onduidelijk. Met behulp van zowel neuropsychologische tests als multi-sequence MRI-scans kunnen we beoordelen of verschillende soorten cerebrovasculaire laesies differentieel geassocieerd zijn met tekorten in specifieke cognitieve domeinen.Het demonstreren van de studieproced...

Video: Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions

The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease

This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of four mountains within a computer-generated landscape is tested using a delayed match-to-sample paradigm. Allocentric spatial memory is assessed by altering the viewpoint, colors and textures between the initially presented and target images.
Allocentric spatial memory is a key function of the hippocampus, one of the earliest brain regions to be affected in Alzheimer&#39;s disease (AD) and impairment of hippocampal function predates the onset of dementia. It was hypothesized that performance on the 4MT would aid the diagnosis of predementia AD, which manifests clinically as Mild Cognitive Impairment (MCI).
The 4MT was applied to patients with MCI, stratified further based on cerebrospinal fluid (CSF) AD biomarker status (10 MCI biomarker positive, 9 MCI biomarker negative), and with mild AD dementia, as well as healthy controls. Comparator tests included tests of episodic memory and attention widely accepted as sensitive measures of early AD. Behavioral data were correlated with quantitative MRI measures of the hippocampus, precuneus and posterior cingulate gyrus.
4MT scores were significantly different between the two MCI groups (p = 0.001), with a test score of &#8804;8/15 associated with 100% sensitivity and 78% specificity for the classification of MCI with positive AD biomarkers, i.e., predementia AD. 4MT test scores correlated with hippocampal volume (r = 0.42) and cortical thickness of the precuneus (r = 0.55).
In conclusion, the 4MT is effective in identifying the early stages of AD. The short duration, easy application and scoring, and favorable psychometric properties of the 4MT fulfil the need for a simple but accurate diagnostic test for predementia AD.

This article describes the 4 Mountains Test (4MT), a hippocampus-dependent test of working allocentric spatial memory. The hippocampus is affected early in Alzheimer's disease (AD) and this article outlines the 4MT methodology and results of patient testing, which demonstrates the value of the 4MT in the diagnosis of pre-dementia AD.

This protocol describes the administration of the 4 Mountains Test (4MT), a short test of spatial memory, in which memory for the topographical layout of ...

Optimized System for Cerebral Perfusion Monitoring in the Rat Stroke Model of Intraluminal Middle Cerebral Artery Occlusion

The translational potential of pre-clinical stroke research depends on the accuracy of experimental modeling. Cerebral perfusion monitoring in animal models of acute ischemic stroke allows to confirm successful arterial occlusion and exclude subarachnoid hemorrhage. Cerebral perfusion monitoring can also be used to study intracranial collateral circulation, which is emerging as a powerful determinant of stroke outcome and a possible therapeutic target. Despite a recognized role of Laser Doppler perfusion monitoring as part of the current guidelines for experimental cerebral ischemia, a number of technical difficulties exist that limit its widespread use. One of the major issues is obtaining a secure and prolonged attachment of a deep-penetration Laser Doppler probe to the animal skull. In this video, we show our optimized system for cerebral perfusion monitoring during transient middle cerebral artery occlusion by intraluminal filament in the rat. We developed in-house a simple method to obtain a custom made holder for twin-fibre (deep-penetration) Laser Doppler probes, which allow multi-site monitoring if needed. A continuous and prolonged monitoring of cerebral perfusion could easily be obtained over the intact skull.

Cerebral perfusion monitoring has been demonstrated to improve accuracy in ischemic stroke models. Technical difficulties often limit the use of this essential tool for cerebrovascular research. In this video, an optimized system is shown to obtain a single or multi-site hemodynamic monitoring during intraluminal middle cerebral artery occlusion in rats.

The translational potential of pre-clinical stroke research depends on the accuracy of experimental modeling. Cerebral perfusion monitoring in animal ...

Medicine

Lesion Explorer: A Video-guided, Standardized Protocol for Accurate and Reliable MRI-derived Volumetrics in Alzheimer's Disease and Normal Elderly

Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are exacerbated when significant brain atrophy and age-related white matter changes (e.g. Leukoaraiosis) are present. Lesion Explorer (LE) is an accurate and reliable neuroimaging pipeline specifically developed to address such issues commonly observed on MRI of Alzheimer's disease and normal elderly. The pipeline is a complex set of semi-automatic procedures which has been previously validated in a series of internal and external reliability tests1,2. However, LE's accuracy and reliability is highly dependent on properly trained manual operators to execute commands, identify distinct anatomical landmarks, and manually edit/verify various computer-generated segmentation outputs.
LE can be divided into 3 main components, each requiring a set of commands and manual operations: 1) Brain-Sizer, 2) SABRE, and 3) Lesion-Seg. Brain-Sizer's manual operations involve editing of the automatic skull-stripped total intracranial vault (TIV) extraction mask, designation of ventricular cerebrospinal fluid (vCSF), and removal of subtentorial structures. The SABRE component requires checking of image alignment along the anterior and posterior commissure (ACPC) plane, and identification of several anatomical landmarks required for regional parcellation. Finally, the Lesion-Seg component involves manual checking of the automatic lesion segmentation of subcortical hyperintensities (SH) for false positive errors.
While on-site training of the LE pipeline is preferable, readily available visual teaching tools with interactive training images are a viable alternative. Developed to ensure a high degree of accuracy and reliability, the following is a step-by-step, video-guided, standardized protocol for LE's manual procedures.

Lesion Explorer (LE) is a semi-automatic, image-processing pipeline developed to obtain regional brain tissue and subcortical hyperintensity lesion volumetrics from structural MRI of Alzheimer's disease and normal elderly. To ensure a high level of accuracy and reliability, the following is a video-guided, standardized protocol for LE's manual procedures.

Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are ...

Brain Infarct Segmentation and Registration on MRI or CT for Lesion-symptom Mapping

In lesion-symptom mapping (LSM), brain function is inferred by relating the location of acquired brain lesions to behavioral or cognitive symptoms in a group of patients. With recent advances in brain imaging and image processing, LSM has become a popular tool in cognitive neuroscience. LSM can provide fundamental insights into the functional architecture of the human brain for a variety of cognitive and non-cognitive functions. A crucial step in performing LSM studies is the segmentation of lesions on brains scans of a large group of patients and registration of each scan to a common stereotaxic space (also called standard space or a standardized brain template). Described here is an open-access, standardized method for infarct segmentation and registration for the purpose of LSM, as well as a detailed and hands-on walkthrough based on exemplary cases. A comprehensive tutorial for the manual segmentation of brain infarcts on CT scans and DWI or FLAIR MRI sequences is provided, including criteria for infarct identification and pitfalls for different scan types. The registration software provides multiple registration schemes that can be used for processing of CT and MRI data with heterogeneous acquisition parameters. A tutorial on using this registration software and performing visual quality checks and manual corrections (which are needed in some cases) is provided. This approach provides researchers with a framework for the entire process of brain image processing required to perform an LSM study, from gathering of the data to final quality checks of the results.

Provided here is a practical tutorial for an open-access, standardized image processing pipeline for the purpose of lesion-symptom mapping. A step-by-step walkthrough is provided for each processing step, from manual infarct segmentation on CT/MRI to subsequent registration to standard space, along with practical recommendations and illustrations with exemplary cases.

In lesion-symptom mapping (LSM), brain function is inferred by relating the location of acquired brain lesions to behavioral or cognitive symptoms in a ...

Assessing Cortical Cerebral Microinfarcts on High Resolution MR Images

Cerebral microinfarcts are frequent findings in the post-mortem human brain, and are related to cognitive decline and dementia. Due to their small sizes it is challenging to study them on clinical MRI scans. It was recently demonstrated that cortical microinfarcts can be depicted with MRI scanners using high magnetic field strengths (7T). Based on this experience, a proportion of these lesions is also visible on lower resolution 3T MRI. These findings were corroborated with ex vivo imaging of post-mortem human brain tissue, accompanied by histopathological verification of possible cortical microinfarcts.
Here an ex vivo imaging protocol is presented, for the purpose of validating MR observed cerebral microvascular pathology with histological evaluation. Furthermore, guidelines are provided for the assessment of cortical microinfarcts on both in vivo 7T and 3T MR images. These guidelines provide researchers with a tool to rate cortical microinfarcts on in vivo images of larger patient samples, to further unravel their clinical relevance in cognitive decline and dementia, and establish these lesions as a novel biomarker of cerebral small vessel disease.

A high resolution ex vivo 7T MR imaging protocol is presented, to perform MR-guided histopathological validation of microvascular pathology in post-mortem human brain tissue. Furthermore, guidelines are provided for the assessment of cortical microinfarcts on in vivo 7T as well as 3T MR images.

Cerebral microinfarcts are frequent findings in the post-mortem human brain, and are related to cognitive decline and dementia. Due to their small sizes ...

Analysis of Cerebral Vasospasm in a Murine Model of Subarachnoid Hemorrhage with High Frequency Transcranial Duplex Ultrasound

Cerebral vasospasm that occurs in the weeks after subarachnoid hemorrhage, a type of hemorrhagic stroke, contributes to delayed cerebral ischemia. A problem encountered in experimental studies using murine models of SAH is that methods for in vivo monitoring of cerebral vasospasm in mice are lacking. Here, we demonstrate the application of high frequency ultrasound to perform transcranial Duplex sonography examinations on mice. Using the method, the internal carotid arteries (ICA) could be identified. The blood flow velocities in the intracranial ICAs were accelerated significantly after induction of SAH, while blood flow velocities in the extracranial ICAs remained low, indicating cerebral vasospasm. In conclusion, the method demonstrated here allows functional, noninvasive in vivo monitoring of cerebral vasospasm in a murine SAH model.

The aim of this manuscript is to present a sonography-based method that allows in vivo imaging of blood flow in cerebral arteries in mice. We demonstrate its application to determine changes in blood flow velocities associated with vasospasm in murine models of subarachnoid hemorrhage (SAH).

Cerebral vasospasm that occurs in the weeks after subarachnoid hemorrhage, a type of hemorrhagic stroke, contributes to delayed cerebral ischemia. A ...

Neuroscience

Motor Dual-Tasks for Gait Analysis and Evaluation in Post-Stroke Patients

Eighteen stroke patients were recruited for this study involving the evaluation of cognition and walking ability and multitask gait analysis. Multitask gait analysis consisted of a single walking task (Task 0), a simple motor dual-task (water-holding, Task 1), and a complex motor dual-task (crossing obstacles, Task 2). The task of crossing obstacles was considered to be equivalent to the combination of a simple walking task and a complex motor task as it involved more nervous system, skeletal movement, and cognitive resources. To eliminate heterogeneity in the results of the gait analysis of the stroke patients, the dual-task gait cost values were calculated for various kinematic parameters. The major differences were observed in the proximal joint angles, especially in the angles of the trunk, pelvis, and hip joints, which were significantly larger in the dual motor tasks than in the single walking task. This research protocol aims to provide a basis for the clinical diagnosis of gait function and an in-depth study of motor control in stroke patients with motor control deficits through the analyses of dual-motor walking tasks.

This paper presents a protocol specifically for dual motor task gait analysis in stroke patients with motor control deficits.

Eighteen stroke patients were recruited for this study involving the evaluation of cognition and walking ability and multitask gait analysis. Multitask ...

Dual-Task Stroop Paradigm for Detecting Cognitive Deficits in High-Functioning Stroke Patients

General clinical cognitive assessment scales are not sensitive enough to cognitive impairment in high-functioning stroke patients. The dual-task assessment has advantages for identifying cognitive deficits in high-functioning stroke patients and has been gradually applied in clinical assessment and cognitive training. Moreover, the Stroop paradigm has higher sensitivity and specificity for attentional assessment than conventional clinical cognitive assessment scales. Therefore, this study presents the dual-task assessment based on the Stroop paradigm to identify cognitive deficits in high-functioning stroke patients. This study demonstrates a single- and dual-task evaluation based on the Stroop paradigm and confirms its feasibility through case experiments and synchronized functional near-infrared spectroscopy evaluation. The Stroop reaction time and correct rate are used as the main indicators to evaluate the cognitive level of the subjects. This study protocol aims to provide new ideas to figure out the ceiling effect in general clinical assessment failure for high-functioning stroke patients.

Clinical assessment scales are notsensitive enough to cognitive dysfunction in high-functioning stroke patients. The dual-task paradigm presents advantages and potential in the assessment and cognitive training of cognitive dysfunction. The study here proposes a dual-task Stroop paradigm to identify cognitive dysfunction in high-functioning stroke patients.

General clinical cognitive assessment scales are not sensitive enough to cognitive impairment in high-functioning stroke patients. The dual-task ...

Evaluation of Capillary and Other Vessel Contribution to Macular Perfusion Density Measured with Optical Coherence Tomography Angiography

Parafoveal circulation of the superficial retinal capillary plexus is usually measured with vessel density, which determines the length of capillaries with circulation, and perfusion density, which calculates the percentage of the evaluated area that has circulation. Perfusion density also considers the circulation of vessels larger than capillaries, although the contribution of these vessels to the first is not usually evaluated. As both measurements are automatically generated by optical coherence tomography angiography devices, this paper proposes a method for estimating the contribution of vessels larger than capillaries by using a coefficient of determination between vessel and perfusion densities. This method can reveal a change in the proportion of perfusion density from vessels larger than capillaries, even when mean values do not differ. This change could reflect compensatory arterial vasodilatation as a response to capillary dropout in the initial stages of retinal vascular diseases before clinical retinopathy appears. The proposed method would allow the estimation of the changes in the composition of perfusion density without the need for other devices.

We describe the evaluation of a coefficient of determination between vessel and perfusion density of the parafoveal superficial capillary plexus to identify the contribution of vessels larger than capillaries to perfusion density.

Parafoveal circulation of the superficial retinal capillary plexus is usually measured with vessel density, which determines the length of capillaries ...

A Needle Model for Vascular Cognitive Impairment Studies in Mice

A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis

Vascular cognitive impairment and dementia (VCID) results from vascular brain injury. Given VCID&#39;s high incidence, which is expected to continue rising as the population ages, it is critical to establish a robust animal model for the disease. This paper presents a novel method of creating a mouse model of VCID that is based on asymmetric bilateral common carotid artery stenosis, which mimics human chronic cerebral hypoperfusion caused by carotid atherosclerosis.
Briefly, common carotid arteries (CCAs) are ligated to different gauge needles (32 G for the right CCA and 34 G for the left CCA) using 7-0 silk sutures followed by immediate needle removal. The remaining suture rings cause persistent blood flow reduction and long-term cognitive impairment associated with white matter injury, microinfarcts, and reactive gliosis, thus closely mimicking the pathogenesis of VCID. Importantly, in this needle model, the clinical representations do not revert with time, providing reliable long-term cognitive impairment. Moreover, the survival rate 24 weeks post surgery was 81.6%, which is higher compared to the other established models of VCID with a similar level of blood flow reduction.
Additional advantages include low material cost and compatibility with MRI to monitor brain injury in live animals since no metal is implanted. The main challenge in employing the needle model of VCID is the requirement for developing advanced surgical skills since mouse CCAs are less than 0.6 mm in diameter and are very fragile. High-quality visual representation of the surgery will thus help researchers to master this technique and advance our understanding of VCID, potentially leading to the development of novel therapeutic modalities to decrease the devastating cognitive decline associated with VCID.

The needle method of asymmetric bilateral common carotid artery stenosis is proposed to create a mouse model for vascular cognitive impairment and dementia. It results in longer-term outcomes compared to previously established models and is compatible with live MRI. Visual representation demonstrating the procedure provides guidance for mastering the surgery.

Vascular cognitive impairment and dementia (VCID) results from vascular brain injury. Given VCID&#39;s high incidence, which is expected to continue ...

Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions

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