Research On Noncontrast Computed Tomography Imaging And Transcriptomics Of Acute Intracerebral Hemorrhage

PART 1: THE NONCONTRAST COMPUTED TOMOGRAPHY IMAGING RESEARCH OF BENIGN INTRACEREBRAL HEMORRHAGEBackground Hematoma growth has been observed in acute intracerebral hemorrhage(ICH)patients and is related to poor outcomes.Therefore,identifying which patients will expand(and which will not)is critical in guiding care.How to identify those at such low risk for expansion that they are excluded from trials of anti-expansion therapies is beneficial to clinical practice and research.Objective To define benign ICH and to investigate the relationship between benign ICH,hematoma growth,and functional outcome.Methods We analyzed a collected study of ICH patients who presented within 6 hours of ICH onset between July 2011 and February 2017.A Follow-up CT scan was performed within 36 hours after the initial CT scan.Benign ICH was operationally defined as homogeneous and regularly shaped small ICH.The presence of benign ICH was judged by two independent reviewers based on the initial CT scan.We defined functional independence as a modified Rankin Scale score of 0-2 at 90 days.The relationship between benign ICH,hematoma growth and functional outcome was assessed by using multivariable logistic regression analyses.Results We included 288 patients in this study and found 48(16.7%)patients with benign ICH.None of the patients with benign ICH had hematoma growth.The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of benign ICH for predicting functional independence at 3 months were 30.7%,96.6%,90.0%,60.0%,and 0.637,respectively.Conclusions Patients with benign ICH are at low risk of hematoma expansion growth and poor functional outcome.These patients may be safe for less intensive monitoring and are unlikely to benefit from therapies aimed at preventing ICH expansion.PART 2: NONCONTRAST COMPUTED TOMOGRAPHY SIGNS PREDICT REVISED HEMATOMA EXPANSION AND POOR OUTCOME IN ACUTE INTRACEREBRAL HEMORRHAGEBackground Noncontrast Computed Tomography(NCCT)markers are the emerging predictors of hematoma expansion(HE)in intracerebral hemorrhage(ICH).However,the relationship between NCCT markers and the dynamic change of hematoma in parenchymal tissues and the ventricular system remains unclear.Objective We aim to propose the definition of RHE(revised hematoma expansion)criteria and to investigate whether the NCCT markers could predict the IVH growth and RHE criteria.We further tested this diagnostic performance of NCCT markers in predicting IVH growth and RHE criteria.Methods We included 314 consecutive ICH patients admitted to our hospital from July 2011 to May 2017.The ICH volumes and intraventricular hemorrhage(IVH)volumes were measured using a semiautomated,computer-assisted technique.Revised hematoma expansion(RHE)was defined by incorporating the original definition of hematoma expansion into IVH growth.Receiver operating characteristic curve analysis was used to compare the performance of the NCCT markers in predicting the IVH growth and revised hematoma expansion.Results Of 314 patients in our study,61(19.4%)had IVH growth and 93(23.9%)patients had RHE.After adjustment for potential confounding variables,blend sign,black hole sign,island sign,and expansion-prone hematoma could independently predict IVH growth and RHE in the multivariate logistic regression analysis,respectively.Expansion-prone hematoma had a higher predictive performance of RHE than any single marker.The diagnostic accuracy of RHE in predicting poor prognosis was significantly higher than that of HE.Conclusions The NCCT markers are independently associated with IVH growth and RHE,respectively.Furthermore,the expansion-prone hematoma has a higher predictive accuracy for the prediction of RHE and poor outcome than any single NCCT marker.These findings may assist in the risk stratification of NCCT signs for predicting active bleeding.PART 3: THE NONCONTRAST COMPUTED TOMOGRAPHY IMAGING RESEARCH OF HYDROCEPHALUS GROWTH IN ACUTE INTRACEREBRAL HEMORRHAGEBackground Intracerebral hemorrhage(ICH)is a major public health burden with high mortality.Hydrocephalus is a well-established neuroimaging of poor prognosis in ICH patients.However,few studies have investigated the dynamic changes of hydrocephalus development during the acute stage of ICH due to these difficulties in calculating the degree of hydrocephalus.Objective To propose a novel definition for hydrocephalus growth and to further describe the association between hydrocephalus growth and poor outcome among patients with ICH.Methods We analyzed consecutive patients who presented within 6 hours after ICH ictus between July 2011 and June 2017.Follow-up CT scans were performed within 36 hours after initial CT scans.The hematoma volume and IVH volumes were calculated using semiautomated,computer-assisted volumetric analysis.The degree of hydrocephalus was evaluated by the hydrocephalus score of Diringer et al.The optimal increase of the hydrocephalus scores between initial and follow-up CT scan was estimated to define hydrocephalus growth.We defined the poor long-term outcome as a modified Rankin Scale of 4-6 at 90 days follow-up.Multivariate logistic regression analysis was performed to investigate the hydrocephalus growth for predicting 30-day mortality,90-day mortality,and poor long-term outcome.Results This study included 321 ICH patients.Of 64 patients with hydrocephalus growth,34(53.1%)patients presented with both concurrent hematoma expansion and intraventricular hemorrhage(IVH)growth.After adjusting for potential confounding factors,hydrocephalus growth independently predicted 30-day mortality,90-day mortality,and 90-day poor long-term outcome in multivariate logistic regression analysis.Hydrocephalus growth showed higher accuracy for predicting 30-day mortality,90-day mortality,and poor long-term outcome than IVH growth or hematoma expansion,respectively.Conclusions Hydrocephalus growth is defined as strongly predictive of short-or long-term mortality and poor outcome at 90 days and might be a potential indicator for assisting clinicians in clinical decision-making.PART 4: POTENTIAL MECHANISM OF HYPERGLYCEMIAAND EARLY NEUROLOGICAL DETERIORATION AFTER INTRACEREBRAL HEMORRHAGE BASED ON TRANSCRIPTOMICS ANALYSISBackground Previous studies have found that admission hyperglycemia in patients with acute intracerebral hemorrhage is associated with neurological impairment,but its underlying mechanism is still unclear.Objective The purpose of this study is to explore the potential effect and mechanism of hyperglycemia in nerve injury after intracerebral hemorrhage by microRNAs(mi RNAs)transcriptomics.Methods We employed the collagenase model of ICH.The hyperglycemia was induced by intraperitoneal injection of 50 % of Dextrose(8 m L/kg)3 hours after ICH.The neurologic impairment was investigated by neurologic deficit scale(NDS).To study the specific mechanisms of hyperglycemia,mi RNA expression in the perihematomal area was investigated by high-throughput RNA sequencing.Mi RNA expression in hyperglycemic ICH animals was compared to normoglycemic mice.Functional annotation analysis was used to indicate potential pathological pathways,underlying observed effects.Finally,polymerase chain reaction(PCR)validation was administered.Results Intraperitoneal injection of dextrose significantly increased blood glucose level.That was associated with aggravation of neurological deficits in hyperglycemic compared to normoglycemic animals.A total of 73 differentially expressed mi RNAs between these two groups were identified via transcriptomics analysis.A series of bioinformatics analyses showed that these were mi RNAs significantly altered in several signaling pathways,of which the hedgehog(Hh)signaling pathway was regarded as the most potential pathway associated with the effect of hyperglycemia on acute ICH.Furthermore,PCR results validated the correlation between mi RNAs and Hh signaling pathway.Conclusions Mi RNAs elevated in the hyperglycemia group may be involved in worsening the neurological function via inhibiting the Hh signaling,which provides a novel molecular physiological mechanism.