Jayapalli Rajiv Bapuraj

Relationship between acute kidney injury and brain MRI findings in asphyxiated newborns after therapeutic hypothermia

Background:We hypothesized that acute kidney injury (AKI) in asphyxiated neonates treated with therapeutic hypothermia would be associated with hypoxic–ischemic lesions on brain magnetic resonance imaging (MRI).Methods:Medical records of 88 cooled neonates who had had brain MRI were reviewed. All neonates had serum creatinine assessed before the start of cooling; at 24, 48, and 72 h through cooling; and then on day 5 or 7 of life. A neonatal modification of the Kidney Disease: Improving Global Outcomes guidelines was used to classify AKI. MRI images were evaluated by a neuroradiologist masked to outcomes. Outcome of interest was abnormal brain MRI at 7–10 d of life.Results:AKI was found in 34 (39%) of 88 neonates, with 15, 7, and 12 fulfilling criteria for stages 1, 2, and 3, respectively. Brain MRI abnormalities related to hypoxia–ischemia were present in 50 (59%) newborns. Abnormal MRI was more frequent in infants from the AKI group (AKI: 25 of 34, 73% vs. no AKI: 25 of 54, 46%; P = 0.012; odds ratio (OR) = 3.2; 95% confidence interval (CI) = 1.3–8.2). Multivariate analysis identified AKI (OR = 2.9; 95% CI = 1.1–7.6) to be independently associated with the primary outcome.Conclusion:AKI is independently associated with the presence of hypoxic–ischemic lesions on postcooling brain MRI.

Distribution and severity of hypoxic–ischaemic lesions on brain MRI following therapeutic cooling: selective head versus whole body cooling

Background Whole body cooling (WBC) cools different parts of the brain uniformly, and selective head cooling (SHC) cools the superficial brain more than the deeper brain structures. In this study, the authors hypothesised that the hypoxic–ischaemic lesions on brain MRI following cooling would differ between modalities of cooling. Aim To compare the frequency, distribution and severity of hypoxic–ischaemic lesions on brain MRI between SHC or WBC. Methods In a single centre retrospective study, 83 infants consecutively cooled using either SHC (n=34) or WBC (n=49) underwent brain MRI. MRI images were evaluated by a neuroradiologist, who was masked to clinical parameters and outcomes, using a basal ganglia/watershed (BG/W) scoring system. Higher scores (on a scale of 0 to 4) were given for more extensive injury. The score has been reported to be predictive of neuromotor and cognitive outcome at 12 months. Results The two groups were similar for severity of depression as assessed by a history of an intrapartum sentinel event, Apgar scores, initial blood pH and base deficit and early neurological examination. However, abnormal MRI was more frequent in the SHC group (SHC 25 of 34, 74% vs WBC 22 of 49, 45%; p=0.0132, OR 3.4, 95% CI 1.3 to 8.8). Infants from the SHC group also had more severe hypoxic–ischaemic lesions (median BG/W score: SHC 2 vs WBC 0, p=0.0014). Conclusions Hypoxic–ischaemic lesions on brain MRI following therapeutic cooling were more frequent and more severe with SHC compared with WBC.

Does phenobarbital improve the effectiveness of therapeutic hypothermia in infants with hypoxic-ischemic encephalopathy?

Objective:To determine whether phenobarbital (PB) given before therapeutic hypothermia to infants with hypoxic-ischemic encephalopathy (HIE) augments the neuroprotective efficacy of hypothermia.Study Design:Records of 68 asphyxiated infants of ⩾36 weeks’ gestation, who received hypothermia for moderate or severe HIE were reviewed. Some of these infants received PB prophylactically or for clinical seizures. All surviving infants had later brain magnetic resonance imaging (MRI). The composite primary outcome of neonatal death related to HIE with worsening multiorgan dysfunction despite maximal treatment, and the presence of post-hypothermia brain MRI abnormalities consistent with hypoxic-ischemic brain injury, were compared between the infants who received PB before initiation of hypothermia (PB group, n=36) and the infants who did not receive PB before or during hypothermia (No PB group, n=32). Forward logistic regression analysis determined which of the pre-hypothermia clinical and laboratory variables predict the primary outcome.Result:The two groups were similar for severity of asphyxia as assessed by Apgar scores, initial blood pH and base deficit, early neurologic examination, and presence of an intrapartum sentinel event. The composite primary outcome was more frequent in infants from the PB group (PB 78% versus No PB 44%, P=0.006, odds ratio 4.5, 95% confidence interval 1.6 to 12.8). Multivariate analysis identified only the PB receipt before initiation of hypothermia (P=0.002, odds ratio 9.5, 95% confidence interval 2.3 to 39.5), and placental abruption to be independently associated with a worse primary outcome.Conclusion:PB treatment before cooling did not improve the composite outcome of neonatal death or the presence of an abnormal post-hypothermia brain MRI, but the long-term outcomes have not yet been evaluated.

Limited short-term prognostic utility of cerebral NIRS during neonatal therapeutic hypothermia

Objective: We evaluated the utility of amplitude-integrated EEG (aEEG) and regional oxygen saturation (rSO2) measured using near-infrared spectroscopy (NIRS) for short-term outcome prediction in neonates with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia. Methods: Neonates with HIE were monitored with dual-channel aEEG, bilateral cerebral NIRS, and systemic NIRS throughout cooling and rewarming. The short-term outcome measure was a composite of neurologic examination and brain MRI scores at 7 to 10 days. Multiple regression models were developed to assess NIRS and aEEG recorded during the 6 hours before rewarming and the 6-hour rewarming period as predictors of short-term outcome. Results: Twenty-one infants, mean gestational age 38.8 ± 1.6 weeks, median 10-minute Apgar score 4 (range 0–8), and mean initial pH 6.92 ± 0.19, were enrolled. Before rewarming, the most parsimonious model included 4 parameters (adjusted R2 = 0.59; p = 0.006): lower values of systemic rSO2 variability (p = 0.004), aEEG bandwidth variability (p = 0.019), and mean aEEG upper margin (p = 0.006), combined with higher mean aEEG bandwidth (worse discontinuity; p = 0.013), predicted worse short-term outcome. During rewarming, lower systemic rSO2 variability (p = 0.007) and depressed aEEG lower margin (p = 0.034) were associated with worse outcome (model-adjusted R2 = 0.49; p = 0.005). Cerebral NIRS data did not contribute to either model. Conclusions: During day 3 of cooling and during rewarming, loss of physiologic variability (by systemic NIRS) and invariant, discontinuous aEEG patterns predict poor short-term outcome in neonates with HIE. These parameters, but not cerebral NIRS, may be useful to identify infants suitable for studies of adjuvant neuroprotective therapies or modification of the duration of cooling and/or rewarming.

Automated subdural hematoma segmentation for traumatic brain injured (TBI) patients

Traumatic brain injury is a serious public health problem in the U.S. contributing to a large portion of permanent disability. However, its early management and treatment could limit the impact of the injury, save lives and reduce the burden of cost for patients as well as healthcare systems. Subdural hematoma is one of the most common types of TBI, which its visual detection and quantitative evaluation are time consuming and prone to error. In this study, we propose a fully auto-mated machine learning based approach for 3D segmentation of convexity subdural hematomas. Textural, statistical and geometrical features of sample points from intracranial region are extracted based on head Computed Tomography (CT) images. Then, a tree bagger classifier is implemented to classify each pixel as hematoma or no-hematoma. Our method yields sensitivity, specificity and area under the receiver operating curve (AUC) of 85:02%, 73:74% and 0:87 respectively.

A morphometric assessment of type I Chiari malformation above the McRae line: A retrospective case-control study in 302 adult female subjects

PURPOSE Type I Chiari malformation (CMI) is a radiologically-defined structural dysmorphism of the hindbrain and posterior cranial fossa (PCF). Traditional radiographic identification of CMI relies on the measurement of the cerebellar tonsils in relation to the foramen magnum with or without associated abnormalities of the neuraxis. The primary goal of this retrospective study was to comprehensively assess morphometric parameters above the McRea line in a group of female CMI patients and normal controls. MATERIAL AND METHODS Twenty-nine morphological measurements were taken on 302 mid-sagittal MR images of adult female CMI patients (n=162) and healthy controls (n=140). All MR images were voluntarily provided by CMI subjects through an online database and control participant images were obtained through the Human Connectome Project and a local hospital system. RESULTS Analyses were performed on the full dataset of adult female MR images and a restricted dataset of 229 participants that were equated for age, race, and body mass index. Eighteen group differences were identified in the PCF area that we grouped into three clusters; PCF structures heights, clivus angulation, and odontoid process irregularity. Fourteen group differences persisted after equating our CMI and control groups on demographic characteristics. CONCLUSION PCF structures reliably differ in adult female CMI patients relative to healthy controls. These differences reflect structural abnormalities in the osseous and soft tissue structures of the clivus, odontoid process, and cerebellum. Clinical and pathophysiological implications are discussed.

Does clinical status 1 week after therapeutic hypothermia predict brain MRI abnormalities

Objective:Hypothermia improves clinical outcomes and brain magnetic resonance imaging (MRI) findings in infants with hypoxic–ischemic encephalopathy. We hypothesized that clinical status following hypothermia predicts brain MRI abnormalities, and helps determine which infants need an early MRI evaluation before discharge. The objective of this study was to determine whether the clinical evaluation 1 week after completion of 72 h of hypothermia treatment predicts the presence of brain MRI abnormalities related to hypoxia–ischemia.Study Design:The medical records of 83 consecutively cooled infants who underwent brain MRI were reviewed. Clinical evaluation by day 10 of life consisted of assessment of oral feeding ability, spontaneous activity, need for mechanical ventilation and a history of clinical seizures. Logistic regression analysis was performed using all four covariates, with an abnormal MRI as the primary outcome. Brain MRI with lesions in both the basal nuclei and the cortex was considered to be severely abnormal.Result:MRI was abnormal in 46 (55%) infants. Univariate analysis identified all of the criteria as being significantly associated with an abnormal MRI. On multivariate analysis, only feeding difficulty (P<0.001, OR 9.5, 95% confidence interval (CI) 3 to 29.8) and a history of clinical seizures (P<0.001, OR 12, 95% CI 3 to 46.5) were significantly associated with an abnormal MRI. The areas under the receiver operating characteristic curve for feeding ability and seizure activity combined (0.86, 95% CI 0.77 to 0.94) indicated good accuracy with respect to the primary outcome. The negative predictive values of feeding difficulty and seizure activity for a severely abnormal MRI were 91% and 96%, respectively.Conclusion:Infants who do not have a history of clinical seizures and who attained full oral feeding by 1 week after hypothermia are unlikely to have an abnormal brain MRI. This simple assessment provides significant prognostic information that can be useful in parental counseling, and may allow selective use of pre-discharge MRI.

Predicting the need for home gavage or g-tube feeds in asphyxiated neonates treated with therapeutic hypothermia

Background:Asphyxiated infants treated with therapeutic cooling can have persistent oral feeding difficulty because of involvement of neural pathways in the brainstem, cortex, and basal ganglia. The goal is to predict the composite adverse outcome of death or persistent oral feeding difficulty using precooling/cooling attributes, and the severity and distribution of hypoxic–ischemic lesions, especially brainstem lesions on post-cooling brain magnetic resonance imaging (MRI).Methods:Retrospective review of 86 asphyxiated infants cooled from January 2006 to August 2014. Persistent feeding difficulty was defined as needing feeding support (gastrostomy tube (g-tube) or home gavage feeds) after discharge. Clinical and laboratory risk factors, and the brain MRI abnormalities including the presence of brainstem lesions were compared between infants with and without adverse outcome using univariate analysis. Significant variables were then analyzed in a stepwise logistic regression (LR) model.Results:Infants with adverse outcome (n = 31, 4 died pre-discharge) had longer hospital stay (26 days, interquartile range (IQR) 19–43 vs. 13 days, IQR 9–20; p < 0.01) and reached goal enteral feeds (oral/gavage) later (11 days vs. 8 days, p < 0.01) compared to 55 infants discharged on full oral feeds. The former infants were more likely to have cord pH ≤ 7.15, severely abnormal neurological examination, bleeding diathesis, continued need for ventilation, and positive MRI findings including brainstem lesions. In LR analysis, brainstem lesions on MRI (p = 0.00, odds ratio 19, 95% confidence interval 4–85) was independently associated with the adverse outcome.Conclusions:Brainstem involvement on post-cooling brain MRI was predictive of adverse outcome. Early identification of these infants may facilitate discussion of home feeding plans between clinicians and parents earlier, thereby potentially reducing the length of hospital stay.

A retrospective 2D morphometric analysis of adult female chiari type I patients with commonly reported and related conditions

Purpose: Researchers have sought to better understand Chiari type I malformation (CMI) through morphometric measurements beyond tonsillar position (TP). Soft tissue and bone structures within the brain and craniocervical junction have been shown to be different for CMI patients compared to healthy controls. Yet, several morphological characteristics have not been consistently associated with CMI. CMI is also associated with different prevalent conditions (PCs) such as syringomyelia, pseudotumor, Ehlers-Danlos syndrome (EDS), scoliosis, and craniocervical instability. The goal of this study was two-fold: (1) to identify unique morphological characteristics of PCs, and (2) to better explain inconsistent results from case-control comparisons of CMI. Methods: Image, demographic, and PC information was obtained through the Chiari1000, a self-report web-accessed database. Twenty-eight morphometric measurements (MMs) were performed on the cranial MR images of 236 pre-surgery adult female CMI participants and 140 female healthy control participants. Custom software was used to measure 28 structures within the posterior cranial fossa (PCF) compartment, craniocervical junction, oral cavity, and intracranial area on midsagittal MR images for each participant. Results: Morphometric analysis of adult females indicated a smaller McRae line length in CMI participants with syringomyelia compared to those without syringomyelia. TP was reduced in CMI participants with EDS than those without EDS. Basion to posterior axial line was significantly longer in CMI participants with scoliosis compared to those without scoliosis. No additional MMs were found to differ between CMI participants with and without a specific PC. Four morphometric differences were found to be consistently different between CMI participants and healthy controls regardless of PC: larger TP and a smaller clivus length, fastigium, and corpus callosum height in CMI participants. Conclusion: Syringomyelia, EDS, and scoliosis were the only PCs that showed significant morphometric differences between CMI participants. Additionally, four midsagittal MR-based MMs were found to be significantly different between healthy controls and CMI participants regardless of the presence of one or more PCs. This study suggests that the prevalence of comorbid conditions are not strongly related to CMI morphology, and that inconsistent findings in the radiographic literature cannot be explained by varying prevalence of comorbid conditions in CMI study samples.

Distribution and Severity of Hypoxic-Ischemic Lesions on Brain MRI Following Therapeutic Cooling: Selective Head Versus Whole Body Cooling

Because whole body cooling (WBC) cools different regions of the brain uniformly, whereas selective head cooling (SHC) cools the superficial brain (cortex) more than the deeper brain (basal ganglia & thalamus, or BGT), we hypothesized that severity of hypoxic-ischemic (HI) lesions following cooling would differ between cooling modalities.Objective: To compare the distribution and the severity of HI lesions on post-cooling brain MRI between infants treated with SHC or WBC.Design Methods: 71 infants consecutively cooled by SHC (n=34) or WBC (n=37) underwent brain MRI at age 7-10 days. Images were evaluated by a masked neuroradiologist. Severity of involvement was assessed by a basal ganglia/watershed (BG/W) scoring system (as proposed by Barkovich and colleagues): 0, normal or no injury; 1, abnormal signal in BGT; 2, abnormal signal in cortex; 3, abnormal signal in cortex not extending beyond the watershed and BGT; 4, abnormal signal in cortex extending beyond the watershed areas and BGT.Results: The 2 Groups had similar Apgar scores, initial blood pH, base deficit, early neurologic examination, and frequency of intrapartum sentinel event. Abnormal MRI was more frequent in the SHC group (SHC 25 of 34, 74% versus WBC 18 of 37, 49%; p= 0.05, OR 2.9, 95% CI 1.1-7.9). The SHC group also had more severe residual HI lesions (median BG/W Score: SHC 4 versus WBC 2, p= 0.008).Conclusions: HI lesions on post-cooling brain MRI were more frequent and severe with SHC compared to WBC. This may reflect a selection bias with more severe cases receiving SHC.