Relationship of Thrombus Length to Number of Stent Retrievals,Revascularization, and Outcomes in Acute Ischemic Stroke

PurposeTo study the relationship between intracranial thrombus length and number of stent retrievals, revascularization rates, and functional outcomes in stroke.Materials and MethodsRetrospective data were collected from consecutive cases of stroke treated with endovascular procedures at a single institution from April 2012–September 2013. Thrombus length was measured in the anterior cerebral circulation. Demographic and clinical details; involved vessels; and procedural details, including the number of devices used and number of retrievals used for each device, were recorded. Revascularization rates and 90-day functional outcomes were recorded.ResultsData regarding the length of thrombus in the anterior cerebral circulation were available for 28 patients. There was no significant association between thrombus length and number of stent retrievals (P = .3780), final thrombolysis in cerebral infarction (TICI) score (P = .4835), or 90-day modified Rankin Scale score (P = .4146). There was a significant difference (P = .0280) between number of retrievals and final TICI score, with lower number of retrieval passes corresponding to higher final TICI scores.ConclusionsThe data suggest no relationship between thrombus length and number of stent retrievals, final TICI score, or functional neurologic outcomes at 90 days in stent retrieval thrombectomy for acute ischemic stroke. These results do not support a predictive value for thrombus length quantification in the evaluation of stroke.     

The silencing of the SWI/SNF subunit and anticancer gene BRM in Rhabdoid tumors

Rhabdoid sarcomas are highly malignant tumors that usually occur in young children. A key to the genesis of this tumor is the mutational loss of the BAF47 gene as well as the widespread epigenetic suppression of other key anticancer genes. The BRM gene is one such epigenetically silenced gene in Rhabdoid tumors. This gene codes for an ATPase catalytic subunit that shifts histones and opens the chromatin. We show that BRM is an epigenetically silenced gene in 10/11 Rhabdoid cell lines and in 70% of Rhabdoid tumors. Moreover, BRM can be induced by BAF47 re-expression and by Flavopiridol. By selective shRNAi knockdown of BRM, we show that BRM re-expression is necessary for growth inhibition by BAF47 re-expression or Flavopiridol application. Similar to lung cancer cell lines, we found that HDAC3, HDAC9, MEF2D and GATA3 controlled BRM silencing and that HDAC9 was overexpressed in Rhabdoid cancer cell lines. In primary BRM-deficient Rhabdoid tumors, HDAC9 was also found to be highly overexpressed. Two insertional BRM promoter polymorphisms contribute to BRM silencing, but only the -1321 polymorphism correlated with BRM silencing in Rhabdoid cell lines. To determine how these polymorphisms were tied to BRM silencing, we conducted ChIP assays and found that both HDAC9 and MEF2D bound to the BRM promoter at or near these polymorphic sites. Using BRM promoter swap experiments, we indirectly showed that both HDAC9 and MEF2D bound to these polymorphic sites. Together, these data show that the mechanism of BRM silencing contributes to the pathogenesis of Rhabdoid tumors and appears to be conserved among tumor types.     

MRI estimates of brain iron concentration in normal aging using quantitative susceptibility mapping

Quantifying tissue iron concentration in vivo is instrumental for understanding the role of iron in physiology and in neurological diseases associated with abnormal iron distribution. Herein, we use recently-developed Quantitative Susceptibility Mapping (QSM) methodology to estimate the tissue magnetic susceptibility based on MRI signal phase. To investigate the effect of different regularization choices, we implement and compare ?₁ and ?₂ norm regularized QSM algorithms. These regularized approaches solve for the underlying magnetic susceptibility distribution, a sensitive measure of the tissue iron concentration, that gives rise to the observed signal phase. Regularized QSM methodology also involves a pre-processing step that removes, by dipole fitting, unwanted background phase effects due to bulk susceptibility variations between air and tissue and requires data acquisition only at a single field strength. For validation, performances of the two QSM methods were measured against published estimates of regional brain iron from postmortem and in vivo data. The in vivo comparison was based on data previously acquired using Field-Dependent Relaxation Rate Increase (FDRI), an estimate of MRI relaxivity enhancement due to increased main magnetic field strength, requiring data acquired at two different field strengths. The QSM analysis was based on susceptibility-weighted images acquired at 1.5 T, whereas FDRI analysis used Multi-Shot Echo-Planar Spin Echo images collected at 1.5 T and 3.0 T. Both datasets were collected in the same healthy young and elderly adults. The in vivo estimates of regional iron concentration comported well with published postmortem measurements; both QSM approaches yielded the same rank ordering of iron concentration by brain structure, with the lowest in white matter and the highest in globus pallidus. Further validation was provided by comparison of the in vivo measurements, ?₁-regularized QSM versus FDRI and ?₂-regularized QSM versus FDRI, which again yielded perfect rank ordering of iron by brain structure. The final means of validation was to assess how well each in vivo method detected known age-related differences in regional iron concentrations measured in the same young and elderly healthy adults. Both QSM methods and FDRI were consistent in identifying higher iron concentrations in striatal and brain stem ROIs (i.e., caudate nucleus, putamen, globus pallidus, red nucleus, and substantia nigra) in the older than in the young group. The two QSM methods appeared more sensitive in detecting age differences in brain stem structures as they revealed differences of much higher statistical significance between the young and elderly groups than did FDRI. However, QSM values are influenced by factors such as the myelin content, whereas FDRI is a more specific indicator of iron content. Hence, FDRI demonstrated higher specificity to iron yet yielded noisier data despite longer scan times and lower spatial resolution than QSM. The robustness, practicality, and demonstrated ability of predicting the change in iron deposition in adult aging suggest that regularized QSM algorithms using single-field-strength data are possible alternatives to tissue iron estimation requiring two field strengths.     

Establishment and characterization of MRT cell lines from genetically engineered mouse models and the influence of genetic background on their development

Malignant rhabdoid tumors (MRTs) are rare, aggressive cancers occuring in young children primarily through inactivation of the SNF5(INI1, SMARCB1) tumor suppressor gene. We and others have demonstrated that mice heterozygous for a Snf5 null allele develop MRTs with partial penetrance. We have also shown that Snf5^+/? mice that lack expression of the pRb family, due to TgT₁₂₁ transgene expression, develop MRTs with increased penetrance and decreased latency. Here, we report that altering the genetic background has substantial effects upon MRT development in Snf5^+/?‐ and TgT₁₂₁;Snf5^+/? mice, with a mixed F1 background resulting in increased latency and the appearance of brain tumors. We also report the establishment of the first mouse MRT cell lines that recapitulate many features of their human counterparts. Our studies provide further insight into the genetic influences on MRT development as well as provide valuable new cell culture and genetically engineered mouse models for the study of CNS‐MRT etiology.     

Arterial spin labeling: Clinical applications

Arterial spin labeling (ASL) is a magnetic resonance imaging perfusion technique that enables quantification of cerebral blood flow (CBF) without the use of intravenous gadolinium contrast. An understanding of the technical basis of ASL and physiologic variations in perfusion are important for recognizing normal variants and artifacts. Pathologic variations in perfusion can be seen in a number of disorders including acute and chronic ischemia, vasculopathy, vascular malformations, tumors, trauma, infection/inflammation, epilepsy and dementia.     

Characteristic phase distribution in the white matter of infants on phase difference enhanced imaging

Background and purpose

The infantile brain is continuously undergoing development. Non-invasive methods to assess the neurological development of infants are important for the early detection of abnormalities. Some microstructures in the brain have been demonstrated via phase difference-enhanced imaging (PADRE), which may reflect myelin-related microstructures. We aimed to assess the white matter (WM) signal distribution in infants using PADRE and compared it with that using T1-weighted images (T1WI) and diffusion tensor imaging (DTI) on magnetic resonance imaging (MRI).

Main inherited neurodegenerative cerebellar ataxias,how to recognize them using magnetic resonance imaging?

Ataxia is a neurodegenerative disease resulting from brainstem, cerebellar, and/or spinocerebellar tracts impairments. Symptoms onset could vary widely from childhood to late-adulthood. Autosomal cerebellar ataxias are considered as one of the most complex group in neurogenetics. In addition to their genetic heterogeneity, there is an important phenotypic variability in the expression of cerebellar impairment, complicating the genetic mutation research. A pattern recognition approach using brain MRI measures of atrophy, hyperintensities and iron-induced hypointensity of the dentate nuclei, could be therefore helpful in guiding genetic research. This review will discuss a pattern recognition approach that, associated with the age at disease onset, and clinical manifestations, may help neuroradiologists differentiate the most frequent profiles of ataxia.     

SWI在胶质母细胞瘤与单发脑转移瘤鉴别中的价值

目的 探讨磁敏感加权成像（SWI）鉴别胶质母细胞瘤与单发脑转移瘤的临床价值。方法 回顾性分析2014年3月至2017年3月经病理证实的21例胶质母细胞瘤与21例脑转移瘤的影像学资料,比较两种肿瘤SWI指标,包括肿瘤内磁敏感信号（ITSS）评分、肿瘤静脉血管数目、出血个数及出血指数;采用受试者工作特征（ROC）曲线分析各指标鉴别诊断的效能。结果 两种肿瘤ITSS评分、出血个数无统计学差异（P>0.05）;但是胶质母细胞瘤静脉血管数目明显高于脑转移瘤（P<0.05）,出血指数明显低于脑转移瘤（P<0.05）。根据ROC曲线分析,肿瘤静脉血管数目为6.5时,鉴别诊断胶质母细胞瘤和脑转移瘤效能最高,曲线下面积为0.751,灵敏度、特异度分别为0.684、0.789;而出血指数为0.9时,鉴别诊断效能最高,曲线下面积为0.715,灵敏度、特异度分别为0.632、0.947。结论 采用SWI可为诊断脑肿瘤提供更多信息,对鉴别胶质母细胞瘤与脑转移瘤具有一定价值。