In vivo detection of cerebral cortical microinfarcts with high-resolution 7T MRI

Cerebrovascular disease has an important role in cognitive decline and dementia. In this context, cerebral microinfarcts are attracting increasing attention, but these lesions could thus far not be detected in vivo. The aim of this study was to try to identify possible cortical microinfarcts on high-resolution 7T in vivo magnetic resonance imaging (MRI) and to perform a histopathologic validation study on similar appearing lesions on 7T ex vivo MRI of postmortem brain tissue. The study population consisted of 22 elderly subjects, who underwent 7T MRI. The fluid attenuated inversion recovery, T₂, and T₁ weighted scans of these subjects were examined for possible cortical microinfarcts. In the ex vivo MRI study, 15 formalin-fixed coronal brain slices of 6 subjects with Alzheimer and vascular pathology were examined and subjected to histopathologic verification. On the in vivo scans, 15 cortical lesions could be identified that were likely to be microinfarcts in 6 subjects. In the postmortem tissue, 6 similar appearing lesions were identified of which 5 were verified as cortical microinfarcts on histopathology. This study provides strong evidence that cortical microinfarcts can be detected in vivo, which will be of great value in further studies into the role of vascular disease in cognitive decline and dementia.     

Cortical microinfarcts on 7T MRI in patients with spontaneous intracerebral hemorrhage

In patients with spontaneous intracerebral hemorrhage (ICH) coexisting abnormalities on brain imaging can provide clues on the etiology of the underlying small vessel disease. We examined cortical cerebral microinfarcts as a novel marker of coexistent vascular damage in ICH. Twelve patients with spontaneous ICH and 15 controls underwent 7Tesla magnetic resonance imaging (MRI). Microinfarcts were present in 9 of 12 patients with spontaneous ICH, and in 5 of 15 controls. This explorative study shows, for the first time, that microinfarcts appear to be a very common vascular comorbidity in spontaneous ICH. Future larger studies should further assess the etiological significance of these lesions.     

Assessing cortical cerebral microinfarcts on iron-sensitive MRI in cerebral small vessel disease

Recent studies suggest that a subset of cortical microinfarcts may be identifiable on T2* but invisible on T1 and T2 follow-up images. We aimed to investigate whether cortical microinfarcts are associated with iron accumulation after the acute stage. The RUN DMC – InTENse study is a serial MRI study including individuals with cerebral small vessel disease (SVD). 54 Participants underwent 10 monthly 3 T MRIs, including diffusion-weighted imaging, quantitative R1 (=1/T1), R2 (=1/T2), and R2* (=1/T2*) mapping, from which MRI parameters within areas corresponding to microinfarcts and control region of interests (ROIs) were retrieved within 16 participants. Finally, we compared pre- and post-lesional values with repeated measures ANOVA and post-hoc paired t-tests using the mean difference between lesion and control ROI values. We observed 21 acute cortical microinfarcts in 7 of the 54 participants (median age 69 years [IQR 66–74], 63% male). R2* maps demonstrated an increase in R2* values at the moment of the last available follow-up MRI (median [IQR], 5 [5–14] weeks after infarction) relative to prelesional values (p = .08), indicative of iron accumulation. Our data suggest that cortical microinfarcts are associated with increased R2* values, indicative of iron accumulation, possibly due to microhemorrhages, neuroinflammation or neurodegeneration, awaiting histopathological verification.     

Cerebral microinfarcts: a systematic review of neuropathological studies

Vascular cognitive impairment is an umbrella term for cognitive dysfunction associated with and presumed to be caused by vascular brain damage. Autopsy studies have identified microinfarcts as an important neuropathological correlate of vascular cognitive impairment that escapes detection by conventional magnetic resonance imaging (MRI). As a frame of reference for future high-resolution MRI studies, we systematically reviewed the literature on neuropathological studies on cerebral microinfarcts in the context of vascular disease, vascular risk factors, cognitive decline and dementia. We identified 32 original patient studies involving 10,515 people. The overall picture is that microinfarcts are common, particularly in patients with vascular dementia (weighted average 62%), Alzheimer's disease (43%), and demented patients with both Alzheimer-type and cerebrovascular pathology (33%) compared with nondemented older individuals (24%). In many patients, multiple microinfarcts were detected. Microinfarcts are described as minute foci with neuronal loss, gliosis, pallor, or more cystic lesions. They are found in all brain regions, possibly more so in the cerebral cortex, particularly in watershed areas. Reported sizes vary from 50 μm to a few mm, which is within the detection limit of current high-resolution MRI. Detection of these lesions in vivo would have a high potential for future pathophysiological studies in vascular cognitive impairment.     

Translating pathology in multiple sclerosis: the combination of postmortem imaging,histopathology and clinical findings

Background – Studies combining postmortem magnetic resonance imaging (MRI) and histopathology have provided important insights into the abnormalities reflected by MRI. Materials and methods – A short overview of these studies applied to multiple sclerosis (MS) is provided in this review, and the Amsterdam postmortem imaging protocol is specifically highlighted. Conclusion – Postmortem MRI and histopathology correlation studies have enabled a direct translation of basic pathology in MS to the clinical setting, and have simultaneously served as a biological validation of new MRI techniques.     

Cortical cerebral microinfarcts on 7T MRI: Risk factors,neuroimaging correlates and cognitive functioning – The Medea-7T study

We determined the occurrence and association of cortical cerebral microinfarcts (CMIs) at 7 T MRI with risk factors, neuroimaging markers of small and large vessel disease, and cognitive functioning. Within the Medea-7T study, a diverse cohort of older persons with normal cognition, patients with vascular disease, and memory clinic patients, we included 386 participants (68 ± 9 years) with available 7 T and 1.5 T/3T brain MRI, and risk factor and neuropsychological data. CMIs were found in 10% of participants and were associated with older age (RR = 1.79 per +10 years, 95%CI 1.28–2.50), history of stroke or TIA (RR = 4.03, 95%CI 2.18–7.43), cortical infarcts (RR = 5.28, 95%CI 2.91–9.55), lacunes (RR = 5.66, 95%CI 2.85–11.27), cerebellar infarcts (RR = 2.73, 95%CI 1.27–5.84) and decreased cerebral blood flow (RR = 1.35 per −100 ml/min, 95%CI 1.00–1.83), after adjustment for age and sex. Furthermore, participants with >2 CMIs had 0.5 SD (95%CI 0.05–0.91) lower global cognitive performance, compared to participants without CMIs. Our results indicate that CMIs on 7 T MRI are observed in vascular and memory clinic patients with similar frequency, and are associated with older age, history of stroke or TIA, other brain infarcts, and poorer global cognitive functioning.     

Intracranial vessel wall lesions on 7T MRI and MRI features of cerebral small vessel disease: The SMART-MR study

The etiology of cerebral small vessel disease (CSVD) is the subject of ongoing research. Although intracranial atherosclerosis (ICAS) has been proposed as a possible cause, studies on their relationship remain sparse. We used 7 T vessel wall magnetic resonance imaging (MRI) to study the association between intracranial vessel wall lesions—a neuroimaging marker of ICAS—and MRI features of CSVD. Within the SMART-MR study, cross-sectional analyses were performed in 130 patients (68 ± 9 years; 88% male). ICAS burden—defined as the number of vessel wall lesions—was determined on 7 T vessel wall MRI. CSVD features were determined on 1.5 T and 7 T MRI. Associations between ICAS burden and CSVD features were estimated with linear or modified Poisson regression, adjusted for age, sex, vascular risk factors, and medication use. In 125 patients, ≥1 vessel wall lesions were found (mean 8.5 ± 5.7 lesions). ICAS burden (per + 1 SD) was associated with presence of large subcortical and/or cortical infarcts (RR = 1.65; 95%CI: 1.12–2.43), lacunes (RR = 1.45; 95% CI: 1.14–1.86), cortical microinfarcts (RR = 1.48; 95%CI: 1.13–1.94), and total white matter hyperintensity volume (b = 0.24; 95%CI: 0.02–0.46). Concluding, patients with a higher ICAS burden had more CSVD features, although no evidence of co-location was observed. Further longitudinal studies are required to determine if ICAS precedes development of CSVD.     

脑小血管病非痴呆患者脑微出血灶和认知功能关系的MRI研究

目的研究小血管病非痴呆患者脑微出血灶和认知功能关系的磁共振成像(MRI)。方法选取2012-01—2014-01我院接收治疗的小血管病非痴呆患者100例,对100例患者进行磁共振梯度回波T2加权成像检查。25例脑微出血阳性患者为观察组,75例脑微出血阴性患者随机选取25例为对照组。采用蒙特利尔认知评估量表(MoCA)、简易精神状态检查量表(MMSE)、画钟试验(CDT)对患者的认知功能进行评价。结果观察组患者的MoCA量表中命名、视空间执行、计算、语言、记忆和概括抽象均低于对照组,观察组MMSE量表和CDT量表评分均低于对照组,观察组脑白质损坏和腔隙性梗死灶数量显著高于对照组,差异具有统计学意义(P0.05)。2组患者的MoCA量表中注意和定向差异无统计学意义(P0.05)。Pearson偏相关分析结果显示脑微出血数量与注意力、视空间执行功能、计算能力呈负相关,与MoCA总分、CDT总分和MMSE总分呈正相关,与语言、命名、延迟记忆、定向力和抽象概括无相关性。结论脑小血管病非痴呆患者脑微出血灶数量与患者的认知功能障碍有一定的相关性,脑微出血灶数量越多,认知功能障碍越严重,可以将脑微出血灶的数量作为诊断早期血管性认知功能障碍的标准。     

Prevalence of stroke in Parkinson's disease: a postmortem study.

The results of previous epidemiological studies of the relationship between Parkinson's disease and stroke have been conflicting; some showing a reduced risk of ischaemic and haemorrhagic stroke during life, and others indicating an increased likelihood of stroke-related death. We compared the frequency of cerebral infarcts and haemorrhages at postmortem in 100 cases of pathologically verified idiopathic Parkinson's disease and 100 age-matched control brains. No significant differences were found in the numbers of infarcts or haemorrhages or stroke-related deaths between the two groups. Our findings do not indicate either a protective effect against stroke, or a greater susceptibility to death from stroke, in the population studied.     

The St. George's dementia bed investigation study: a comparison of clinical and pathological diagnosis.

Sixty-four elderly patients who had been admitted to the St. George's Hospital Alzheimer's disease evaluation project during 1981-1989 were followed up to postmortem examination. Comparison between clinical diagnoses and neuropathological diagnoses indicated positive predictive values for the antemortem diagnoses of 50-67%. Existing clinical criteria may not be accurate enough to permit firm antemortem diagnosis of older people for either research or clinical purposes.     

Comparison of Premortem Magnetic Resonance Imaging and Postmortem Autopsy Findings of a Cortical Microinfarct

An 85-year-old woman diagnosed with amyotrophic lateral sclerosis died of pneumonia and was autopsied. Magnetic resonance imaging (MRI) performed 16 days before death revealed an intracortical high-intensity lesion in her right temporal cortex on three-dimensional (3D)-double inversion recovery (DIR) and 3D-fluid-attenuated inversion recovery (FLAIR) images. Histopathological examination indicated a cortical microinfarct (CMI) juxtaposed to cerebral amyloid angiopathy. Recently, in vivo detection of CMIs using 3D-DIR and 3D-FLAIR on 3-tesla MRI has been reported, and postmortem MRI study confirmed the presence of CMIs. This is the first case study to compare CMI findings detected upon premortem MRI to the CMI itself discovered upon postmortem neuropathological examination.     

Association of white matter lesions and brain atrophy with the development of dementia in a community: the Hisayama Study

Aim

To investigate the association of white matter lesions volume (WMLV) levels with dementia risk and the association between dementia risk and the combined measures of WMLV and either total brain atrophy or dementia-related gray matter atrophy in a general older population.

Methods

One thousand one hundred fifty-eight Japanese dementia-free community-residents aged ≥65 years who underwent brain magnetic resonance imaging were followed for 5.0 years. WMLV were segmented using the Lesion Segmentation Toolbox. Total brain volume (TBV) and regional gray matter volume were estimated by voxel-based morphometry. The WMLV-to-intracranial brain volume ratio (WMLV/ICV) was calculated, and its association with dementia risk was estimated using Cox proportional hazard models. Total brain atrophy, defined as the TBV-to-ICV ratio (TBV/ICV), and dementia-related regional brain atrophy defined based on our previous report were calculated. The association between dementia risk and the combined measures of WMLV/ICV and either total brain atrophy or the number of atrophied regions was also tested.

Results

During the follow-up, 113 participants developed dementia. The risks of dementia increased significantly with higher WMLV/ICV levels. In addition, dementia risk increased additively both in participants with higher WMLV/ICV levels and lower TBV/ICV levels and in those with higher WMLV/ICV levels and a higher number of dementia-related brain regional atrophy.

Conclusion

The risk of dementia increased significantly with higher WMLV/ICV levels. An additive increment in dementia risk was observed with higher WMLV/ICV levels and lower TBV/ICV levels or a higher number of dementia-related brain regional atrophy, suggesting the importance of prevention or control of cardiovascular risk factors.     

Evaluation of postcontrast images of intracranial tumors at 7T and 3T MRI: An intra-individual comparison study

Aim

This study aimed to evaluate the diagnostic value of ultrahigh-field magnetic resonance imaging (MRI) for brain tumors in clinical practice.

Methods

Thirty patients with brain tumors underwent 7- and 3-T MRI. The performance and diagnostic confidence of 7- and 3-T MRI in the visualization of tumor details such as internal structure and feeding artery were evaluated by radiologists. Contrast-enhanced region performance and tumor detail diagnostic confidence score (DCS) were calculated and compared between 7 and 3T using Wilcoxon rank sum test.

Results

In 19 with obvious enhancement and 11 cases without obvious enhancement, 7- and 3-T MRI showed similar performance. The tumors' internal structure and feeding artery were more clearly depicted by 7-T MRI (62.2% and 54.4%, respectively) than by 3-T MRI (2.2% and 6.7%, respectively). Furthermore, the mean DCSs of both internal structure and feeding artery were higher at 7T than at 3T (internal structure: 16.29 ± 9.67 vs. −5.79 ± 4.12, p = 0.028; feeding artery: 21.96 ± 6.93 vs. 4.46 ± 7.07, p = 0.028). The DCS was more significantly improved in the senior radiologist group.

Conclusion

Better visualization of brain tumor details and higher tumor detail diagnostic confidence can be obtained with 7-T MRI.     

脑小血管病患者伴发非痴呆血管性认知功能损害情况及尼莫地平疗效的研究

目的探讨脑小血管病(cerebral small vessel disease,SVD)不同亚型伴发非痴呆血管性认知功能损害的情况,评价尼莫地平对SVD的疗效。方法选择SVD患者118例,包括52例腔隙灶脑梗死(LI)和66例白质疏松(WML)患者。分别将LI组和WML组患者随机分组为治疗组(基础治疗加尼莫地平治疗)和对照组(基础治疗),进行6个月治疗。治疗前后对所有患者采用蒙特利尔认知评估量表(MoCA)、简易智能状态检查表(MMSE)、语义分类流畅测验(动物)、Stroop测验(计算错误数)、画钟试验、积木测验、数字广度顺背测验、数字符号测验、逻辑记忆亚测验和再生亚测验进行认知功能评价,并比较各组患者治疗前后认知功能评分。结果治疗前,LI组患者语义分类流畅测验(动物)、数字符号测验、逻辑记忆亚测验、视觉再生亚测验、MoCA、MMSE评分显著高于WML组患者,Stroop测验得分显著低于WML组患者。经过6个月治疗后,LI组和WML组患者中的对照组治疗前后各项认知功能评分均没有统计学差异(P>0.05)。LI组患者中治疗组MoCA、画钟试验和数字广度顺背测验得分升高,Stroop测验得分下降(均P<0.05);WML组患者中治疗组MoCA、MMSE、画钟试验、数字广度顺背测验和视觉再生亚测验得分升高,Stroop测验得分下降(均P<0.05)。结论 SVD两个亚型伴发非痴呆血管性认知功能损害情况不同,LI患者损害程度比WML患者轻。尼莫地平治疗可较好的改善患者的执行功能、视空间结构能力和注意力。     

In vivo visualization of senile-plaque-like pathology in Alzheimer's disease patients by MR microscopy on a 7T system.

BACKGROUND: Microscopic application of magnetic resonance imaging (MRI) has entered the era of clinical application. One of the most important targets is the visualization of pathological findings such as senile plaques (SP), in vivo, in patients with Alzheimer's disease (AD). Such an application provides not only the most accurate diagnostic tool for clinicians but also a solid basis for scientists for developing effective treatment and preventive strategies for AD. METHODS: Focused microscopic studies were performed on parietal association cortex at the level of the centrum semiovale identified on conventional axial slices using a system constructed based on General Electric Signa LX (Waukesha, WI) equipped with a 900-mm clear bore superconducting magnet operating at 7.0 T in 10 patients (67-83-year old, five males, five females) who fulfilled the NINCD and the SADRDA criteria for probable AD, 10 age-matched controls (71-85-year old, five males, five females), and 20 young adults (22-35-year old, 10 males, 10 females) using a susceptibility weighted imaging (SWI) algorithm. RESULTS: SWI microscopy consistently provided images with SP-like pathology extending within the entire parietal cortex in all cases of AD and 2 out of 10 age-matched volunteers. CONCLUSIONS: Although the precise mechanisms leading to the higher susceptibility rendering SP-like pathology observable within the cortical mantle are not totally understood, the study unambiguously demonstrated that MR microscopy is capable of directly visualizing cortical pathology in AD patients in vivo.     

甘露醇治疗脑血管病性脑水肿的MRI研究

目的 评价甘露醇治疗脑水肿的最佳方案。方法 测定MRI T_1和T_2值及水肿区大小,观察甘露醇用药前后对脑血管病性脑水肿的治疗作用。急性脑血管病14例,分为A、B二组。A组7例为发病后1～3天,平均已用甘露醇2～9次;B组7例为发病后4～7天已用甘露醇8～18次。 结果 A组病人用甘露醇后水肿区减小,T_1和T_2值下降,以水肿周边区为主。B组病人用甘露醇后水肿区增大,T_1和T_2值增加,以水肿中心区为主。结论 提示甘露醇在临床上只能在病情急需时短期应用。其脱水作用主要表现在水肿区的周边部分,若加重脑水肿主要表现在水肿区的中心部位。