Cerebral Small Vessel Disease Lesions Research Articles

Quantitative Analysis of Multimodal MRI Markers and Clinical Risk Factors for Cerebral Small Vessel Disease Based on Deep Learning.

Cerebral small vessel disease lacks specific clinical manifestations, and extraction of valuable features from multimodal images is expected to improve its diagnostic accuracy. In this study, we used deep learning techniques to segment cerebral small vessel disease imaging markers in multimodal magnetic resonance images and analyze them with clinical risk factors. We recruited 211 lacunar stroke patients and 83 control patients. The patients' cerebral small vessel disease markers were automatically segmented using a V-shaped bottleneck network, and the number and volume were calculated after manual correction. The segmentation results of the V-shaped bottleneck network for white matter hyperintensity and recent small subcortical infarction were in high agreement with the ground truth (DSC>0.90). In small lesion segmentation, cerebral microbleed (average recall=0.778; average precision=0.758) and perivascular spaces (average recall=0.953; average precision=0.923) were superior to lacunar infarct (average recall=0.339; average precision=0.432) in recall and precision. Binary logistic regression analysis showed that age, systolic blood pressure, and total cerebral small vessel disease load score were independent risk factors for lacunar stroke (P<0.05). Ordered logistic regression analysis showed age was positively correlated with cerebral small vessel disease load score and total cholesterol was negatively correlated with cerebral small vessel disease score (P<0.05). Lacunar stroke patients exhibited higher cerebral small vessel disease imaging markers, and age, systolic blood pressure, and total cerebral small vessel disease score were independent risk factors for lacunar stroke patients. V-shaped bottleneck network segmentation network based on multimodal deep learning can segment and quantify various cerebral small vessel disease lesions to some extent.

Association between Cerebral Small Vessel and Alzheimer's Disease

뇌소혈관질환은 뇌 자기공명영상에서 흔히 관찰되는 혈관성 변화로 뇌백질 고신호강도, 뇌미세출혈, 열공성 경색, 혈관주위공간 등을 포함한다. 이러한 혈관성 변화가 알츠하이머병(Alzheimer’s disease; 이하 AD)의 발병 및 진행과 관련되어 있고, 대표 병리인 베타 아밀로이드 및 타우 단백의 침착과도 연관되어 있다는 증거들이 축적되고 있다. 혈관성 변화는 생활 습관 개선이나 약물 치료를 통해 예방과 개선이 가능하기 때문에 뇌소혈관질환과 AD 및 AD 생체지표의 관련성을 연구하는 것이 중요하다. 본 종설에서는 AD와 AD 생체지표에 대해 간략히 소개하고, AD와 혈관성 변화의 관련성에 대해 축적된 증거들을 제시한 다음, 뇌소혈관질환의 병태 생리와 MR 영상 소견을 설명하고자 한다. 또 뇌소혈관질환과 AD 진단의 위험도 및 AD 생체지표와의 관련성에 대한 기존 연구 결과들을 정리하고자 한다.

Abstract P52: Temporal Progression of Cerebral Small Vessel Disease Lesions on Brain Magnetic Resonance Imaging in Spontaneously Hypertensive Stroke Prone Rats

Introduction: Spontaneously Hypertensive Rats- Stroke Prone (SHRSP) are a relevant model for human cerebral small vessel disease (cSVD). However, data are still lacking regarding the neuroimaging correlates of cSVD lesions in SHRSP and their temporal evolution in relationship to histological findings. Methods: 40 SHRSP and 40 Wistar Kyoto control (WKY) male rats were divided into 4 groups (10 WKY and 10 SHRSP) per group. Systolic blood pressure (SBP) was measured using tail-cuff device, weekly. Select animals of each group had brain MRI at 9.4T machine at 7, 16, 24, and 32 weeks of age. Volumetric analysis was completed using manual segmentation of the total brain, ventricles and bilateral hippocampi. Following MRI, brain histology was completed at the same time points. Results: At 6 weeks, SBP was similar (WKY 123.8±0.1 vs SHRSP 130.7±3.2, P=0.09). SHRSP developed hypertension between 9-11 weeks of age and maintained it throughout the experiment (SBP at 31 weeks: WKY 138.1±6 vs SHRSP 169.1±6.7, p=0.0006). At 7 weeks, brain MRI was normal in SHRSP and WKY. Histology was largely unremarkable except for few areas of red blood cell extravasation in couple of SHRSP. At 16 weeks, MRI was normal in WKY and it showed small subcortical hyperintensity on T2 sequences in one SHRSP while histology showed microbleeds (MBs) in 85% of SHRSP. At 24 weeks, brain MRI consistently identified subcortical hyperintensities in SHRSP and H&amp;E showed MBs in all SHRSP in addition to hemosiderin deposition and arteriosclerosis. LFB staining showed areas of demyelination in the corpus callosum. At 32 weeks, SHRSP had hydrocephalus and H&amp;E showed widespread hemosiderin deposition. Volumetric analysis showed larger ventricles in SHRSP (SHRSP 42.3±18.1 ml vs WKY 28.4±7.2 ml, p=0.013) and ventricle size significantly increased with age in SHRSP. Hippocampal and brain volumes were similar in both groups (hippocampal volume: WKY 84.5±8.1 ml vs SHRSP 81.6±2.6 ml, p=0.39; brain volume WKY 2103.4±100.4 ml vs SHRSP 2169.6 ±164.2 ml, p=0.2). Conclusions: SHRSP develop cSVD histological changes early in life and brain MRI showed consistent abnormalities at a later time point. These results have implications in defining cSVD phenotypes in SHRSP in future mechanistic studies.

Confluent White Matter in Progression to Alzheimer Dementia.

Alongside Alzheimer disease pathology, cerebral small vessel disease (CSVD) contributes to the differential progression rates from mild cognitive impairment (MCI) to dementia. Hence, identification of specific type of CSVD lesions that influence progression is needed. The objective of this study was to evaluate the role of silent CSVD in the progression from MCI to dementia and if confluent white matter hyperintensities (WMHs) pose a higher risk for progression in the clinical setting. Patients with MCI with baseline magnetic resonance imaging and longitudinal follow-up were evaluated. WMH were quantified using visual scoring at baseline (all subjects) and at end of study period (subgroup). Influences of baseline total WMH, baseline confluent WMH, and increase of WMH on progression from MCI to dementia were analyzed. A total of 200 patients with a mean age of 67.9 (SD 8.7) years were evaluated. Progression to dementia was significantly higher among patients with MCI with confluent WMH (55.7% vs. 32.3%; P<0.001). The odds ratio of a patient with confluent WMH progressing to dementia was 2.66. The annual decline in Mini Mental State Examination was significantly higher in those with confluent WMH lesions (-1.60 vs. -1.20; P=0.010). In the subgroup with follow-up magnetic resonance imaging (n=70), patients who demonstrated an increase in WMH had greater decline in annual Mini Mental State Examination scores (-1.79 vs. -0.59; P=0.054). Confluent WMH lesions in MCI are associated with higher rates of progression to dementia.

Expression and Significance of MicroRNA155 in Serum of Patients with Cerebral Small Vessel Disease.

ObjectiveThis study aimed to investigate the changes and significance of microRNA155 levels in serum of patients with cerebral small vessel disease (CSVD). MethodsThirty patients with CSVD who met the inclusion criteria were selected and divided into eight patients with lacunar infarction (LI) group and 22 patients with multiple lacunar infarction (MLI) combined with white matter lesions (WML) group according to the results of head magnetic resonance imaging (MRI). Thirty samples from healthy volunteers without abnormalities after head MRI examination were selected as the control group. The levels of serum microRNA155 in each group were determined by real-time polymerase chain reaction, and the correlation between microRNA155 in the serum of patients with CSVD and the increase of imaging lesions was analyzed by Spearman correlation analysis. ResultsCompared with the control group, the serum microRNA155 level in the LI group, MLI combined with WML group increased, the difference was statistically significant (p<0.05); serum microRNA155 level was positively correlated with the increase of imaging lesions (p<0.05). ConclusionThe change of serum microRNA155 level in patients with CSVD may be one of its self-protection mechanisms, and the intensity of this self-protection mechanism is positively correlated with the number of CSVD lesions.

Abstract 40: Time Course of Cerebral Small Vessel Disease Lesions and Sensory Motor Changes in Spontaneously Hypertensive Stroke Prone Rats

Introduction: Animal models of human cerebral small vessel disease (CSVD) are important for the study of the disease underlying mechanisms and testing therapeutic interventions. Spontaneusly Hypertensive Rats - Stroke Prone (SHRSP) are used as an animal model of human CSVD. However, there is a lack of data regarding the time course of cognitive and motor impairment. Methods: Male age-matched SHRSP and Wistar Kyoto rats (WKY) were studied. Sensorimotor testing (open field test) and tail-cuff systolic blood pressure (SBP) measurements (Visitech Systems, Inc.) were performed weekly starting from 6 until 24 weeks of age. Brain MRI at 7 and 24 weeks was acquired using a 9.4T MRI system. Brain histology was completed at the same time points. Statistical analysis was performed using a linear mixed model with repeated measurements. P&lt; 0.05 was considered significant. Results: 20 SHRSP and 20 WKY male rats were studied. 10 per group were euthanized following brain MRI at 7 weeks and the rest were followed until 24 weeks. SHRSP weighed on average 30 grams less than WKY throughout the study (P=0.0003). At 7 weeks SBP was not different (WKY 106.6±5.4 vs SHRSP 120.8±5.4, P=0.06). SHRSP started to develop hypertension at 9-12 weeks and maintained hypertension until 24 weeks (average group difference across time P&lt;0.0001; SBP at 21 weeks WKY 134.8±5.4 vs SHRSP 168.9±5.4, P&lt;0.0001). Sensorimotor testing showed higher total distance travelled (TDT) at 7 weeks in SHRSP that trended down with ageing. Both groups became similar at 21 weeks (TDT: at 7 weeks WKY 3.78±1.3 vs SHRSP 7.8±1.3, P =0.037; at 21 weeks: WKY 4±1.3 vs SHRSP 4.4±1.3, P=0.83; average group difference across time P=0.014). Brain MRI was normal at 7 weeks, but small white matter hyperintensities were seen at 24 weeks. Brain Histology showed normal histology on hematoxylin &amp; eosin staining at 7 weeks in both groups, while at 24 weeks SHRSP showed CSVD histopathological changes including microbleed formation, homeostasis and vascular hyalinosis. Conclusions: SHRSP develops hypertension, sensorimotor deficits and CSVD pathology as they age suggesting their utility as human CSVD model. Intervention time points should be selected carefully in future therapeutic drug interventions.

Cerebral Small Vessel Disease and Stage 1 Hypertension Defined by the 2017 American College of Cardiology/American Heart Association Guidelines.

Although the American College of Cardiology/American Heart Association guidelines have introduced a novel definition of hypertension in their 2017 hypertension guidelines, the influence of novel stage 1 hypertension on cerebrovascular diseases remains unclear. In this study, we evaluated the relationship between stage 1 hypertension, as defined by the 2017 American College of Cardiology/American Heart Association guidelines and cerebral small vessel disease in a healthy population. We assessed consecutive health checkup participants without the use of antihypertensive medication between 2006 and 2013. White matter hyperintensity volumes were rated using semiautomated quantitative methods. The presence of lacunes, cerebral microbleeds, and enlarged perivascular spaces was also measured as cerebral small vessel disease lesions. We classified the blood pressure of all participants according to the 2017 American College of Cardiology/American Heart Association guidelines. A total of 2460 participants were evaluated. In adjusted linear and logistic regression analyses, stage 1 hypertension was independently associated with white matter hyperintensity volume (β=0.158; 95% CI, 0.046-0.269; P=0.006), presence of lacune (adjusted odds ratio, 1.66; 95% CI, 1.00-2.73; P=0.048), and deep cerebral microbleeds (adjusted odds ratio, 2.50, 95% CI, 1.08-5.79; P=0.033). Stage 2 hypertension showed higher coefficients or adjusted odds ratio values and lower P values in all analyses of white matter hyperintensity volumes, lacunes, and deep cerebral microbleeds, indicating dose-response effects across blood pressure categories. Stage 1 hypertension according to the 2017 American College of Cardiology/American Heart Association guidelines is associated with cerebral small vessel disease lesions, especially in white matter hyperintensity lesions, lacunes, and deep cerebral microbleeds.

Abstract TP563: White Matter Hyperintensities are Associated With Intracranial Internal Carotid Artery Calcifications in a Cohort of Patients With Acute Ischemic Stroke or Transient Ischemic Attack

Introduction: Previous studies of the relationship between cerebral small vessel disease (CSVD) lesions and carotid artery (CA) calcifications have yielded conflicting results. Hypothesis: We hypothesized that intracranial ICA (ICICA) calcifications are most closely associated with CSVD in comparison to extracranial ICA (ECICA) and common CA (CCA) calcifications. Methods: Acute ischemic stroke and transient ischemic attack patients were recruited into a hospital-based prospective stroke registry. Total CSVD burden score including white matter hyperintensity (WMH), lacunes, microbleeds (MBs) and enlarged perivascular spaces (PVS) was measured according to Staals et al. Fazekas scale was used to rate the periventricular and deep WMH (PVMH and DWMH respectively). ICICA calcifications were measured on plain head CT scan according to Subedi et al. ECICA and CCA calcifications were measured according to Yamada et al on the neck CT angiography. Univariate analyses were used to test the relationship between CSVD lesions and CA calcifications. Binary and ordered logistic regression analyses were performed to adjust for the effect of age, sex, race, history of hypertension, diabetes and current smoking for the variables that showed significance in the univariate analyses. Results: 141 patients (age 64.5±15.3, 49% females, total CSVD score 1.6±1.4, ICICA, ECICA and CCA calcification scores were 7.8±9.9, 10.3±13.4 and 2.1±6.9, respectively). In Univariate analyses, ICICA calcification score showed significant relationships with PVMH, DWMH, lacunes, MBs and total CSVD scores ( P values: &lt;0.0001, 0.0005, 0.0078, 0.049 and 0.0026 respectively). ECICA calcification score showed significant relationships with PVWMH and DWMH (P values: 0.0062 and 0.0332, respectively) while CC calcification score showed significant relationships with PVMWH, DWMH, MBs and PVS (P values: 0.0008, 0.034, 0.045 and 0.013). Multivariate analyses showed significant relationships only for PVWMH and DWMH with ICICA calcification (P values: 0.008 and 0.05, respectively). Conclusions: ICICA calcifications are most closely linked to PVMW and DWMH. Further studies are required to investigate the pathophysiological mechanisms behind this relationship.

Cognitive Impact of Cerebral Small Vessel Disease Changes in Patients With Hypertension.

Hypertension is one of the principal risk factors for cerebral small vessel disease progression and cognitive impairment. We aimed to investigate how changes in cerebral small vessel disease lesions relate to cognitive decline and incident mild cognitive impairment in hypertensive patients. Data were obtained from the ISSYS cohort (Investigating Silent Strokes in Hypertensives: a Magnetic Resonance Imaging Study)-a longitudinal population-based study on hypertensive patients aged 50 to 70 years without dementia and stroke at baseline. Patients underwent a brain magnetic resonance imaging, a cognitive screening test, and cognitive diagnosis (normal aging or mild cognitive impairment) at baseline and follow-up. We evaluated incident lacunar infarcts and cerebral microbleeds. Changes in the periventricular and deep white matter hyperintensities (WMH) were qualitatively defined as none, minor, or marked. We followed up 345 patients (median age, 65 [61-68]; 55.4% men) for 3.95 (3.83-4.34) years. Incident mild cognitive impairment was diagnosed in 9.1% of the sample. Considering the progression of cerebral small vessel disease, the prevalence of incident infarcts was 6.1% and that of incident cerebral microbleeds was 5.5%; progression of periventricular WMH was 22% and that of deep WMH was 48%. Patients with marked progression of periventricular WMH showed a significant decrease in global cognition compared with patients without progression (adjusted mean [SE], -0.519 [0.176] versus 0.057 [0.044], respectively; P value=0.004) and a higher risk of incident mild cognitive impairment (OR, 6.184; 95% CI, 1.506-25.370; P value=0.011). Therefore, our results indicate that hypertensive patients with progression of periventricular WMH have higher odds of cognitive impairment, even in the early stages of cognitive decline.

Multiple sclerosis: High prevalence of the 'central vein' sign in white matter lesions on susceptibility-weighted images.

Purpose The aim of this study was to determine the occurrence and distribution of the 'central vein' sign in white matter lesions on susceptibility-weighted magnetic resonance images in patients with multiple sclerosis (MS) and cerebral small vessel disease (CSVD). Materials and methods T2-weighted and fluid-attenuated inversion recovery magnetic resonance images of 19 MS patients and 19 patients affected by CSVD were analysed for the presence and localisation of focal hyperintense white matter lesions. Lesions were subdivided into periventricular or non-periventricular (juxtacortical, subcortical, deep white matter and cerebellar) distributed. The number and localisation of lesions presenting with the central vein sign were recorded and compared between MS and CSVD lesions. Results A total of 313 MS patients and 75 CSVD lesions were identified on T2-weighted and fluid-attenuated inversion recovery magnetic resonance images. The central vein sign was found in 128 MS lesions (40.9%), and the majority of them (71/128, 55.5%) had a periventricular distribution. The central vein sign was found in 22 out of 75 (29.3%) CSVD lesions, and periventricular distribution was seen in six out of 22 (27.2%) CSVD lesions. The difference in the proportion of white matter hyperintense lesions that presented with the central vein sign on susceptibility-weighted images in patients with MS and CSVD was statistically different, and a significantly higher number of MS patients presented with lesions with the central vein sign compared to CSVD patients. Conclusion The presence of the central vein sign on susceptibility-weighted images for MS lesions improves the understanding of the periventricular distribution of MS lesions and could contribute as adjunctive diagnostic criteria for MS disease.