Assessment of factors that confound MRI and neuropathological correlation of human postmortem brain tissue

In spite of considerable technical advance in MRI techniques, the optical resolution of these methods are still limited. Consequently, the delineation of cytoarchitectonic fields based on probabilistic maps and brain volume changes, as well as small-scale changes seen in MRI scans need to be verified by neuronanatomical/neuropathological diagnostic tools. To attend the current interdisciplinary needs of the scientific community, brain banks have to broaden their scope in order to provide high quality tissue suitable for neuroimaging- neuropathology/anatomy correlation studies. The Brain Bank of the Brazilian Aging Brain Research Group (BBBABSG) of the University of Sao Paulo Medical School (USPMS) collaborates with researchers interested in neuroimaging-neuropathological correlation studies providing brains submitted to postmortem MRI in-situ. In this paper we describe and discuss the parameters established by the BBBABSG to select and to handle brains for fine-scale neuroimaging-neuropathological correlation studies, and to exclude inappropriate/unsuitable autopsy brains. We tried to assess the impact of the postmortem time and storage of the corpse on the quality of the MRI scans and to establish fixation protocols that are the most appropriate to these correlation studies. After investigation of a total of 36 brains, postmortem interval and low body temperature proved to be the main factors determining the quality of routine MRI protocols. Perfusion fixation of the brains after autopsy by mannitol 20% followed by formalin 20% was the best method for preserving the original brain shape and volume, and for allowing further routine and immunohistochemical staining. Taken to together, these parameters offer a methodological progress in screening and processing of human postmortem tissue in order to guarantee high quality material for unbiased correlation studies and to avoid expenditures by post-imaging analyses and histological processing of brain tissue.

Late Gadolinium Enhancement Magnetic Resonance Imaging in the Diagnosis and Prognosis of Endomyocardial Fibrosis Patients

Background-Endocardial fibrous tissue (FT) deposition is a hallmark of endomyocardial fibrosis (EMF). Echocardiography is a first-line and the standard technique for the diagnosis of this disease. Although late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) allows FT characterization, its role in the diagnosis and prognosis of EMF has not been investigated. Methods and Results-Thirty-six patients (29 women; age, 54 +/- 12 years) with EMF diagnosis after clinical evaluation and comprehensive 2-dimensional Doppler echocardiography underwent cine-CMR for assessing ventricular volumes, ejection fraction and mass, and LGE-CMR for FT characterization and quantification. Indexed FT volume (FT/body surface area) was calculated after planimetry of the 8 to 12 slices obtained in the short-axis view at end-diastole (mL/m(2)). Surgical resection of FT was performed in 16 patients. In all patients, areas of LGE were confined to the endocardium, frequently as a continuous streak from the inflow tract extending to the apex, where it was usually most prominent. There was a relation between increased FT/body surface area and worse New York Heart Association functional class and with increased probability of surgery (P<0.05). The histopathologic examination of resected FT showed typical features of EMF with extensive endocardial fibrous thickening, proliferation of small vessels, and scarce inflammatory infiltrate. In multivariate analysis, the patients with FT/body surface area >19 mL/m(2) had an increased mortality rate, with a relative risk of 10.8. Conclusions-Our study provides evidence that LGE-CMR is useful in the diagnosis and prognosis of EMF through quantification of the typical pattern of FT deposition. (Circ Cardiovasc Imaging. 2011;4:304-311.)

Hematological indices at birth in relation to arterial and venous Doppler in small-for-gestational-age fetuses

Objective. To correlate Doppler results with hematological indices at birth in small-for-gestational-age (SGA) fetuses. Design. Prospective study. Setting. Tertiary teaching hospital, Sao Paulo, Brazil. Population. One hundred singleton pregnancies with SGA fetuses of > 27 weeks gestational age. Methods. All women had Doppler velocimetry of the umbilical arteries, middle cerebral artery, and ductus venosus within < 72 hours prior to delivery. After birth, umbilical artery blood was collected for hematological analysis. Main outcome measures. The association between fetal Doppler velocimetry pulsatility index (PI) and some hematological indices. Results. Umbilical artery PI showed a positive correlation with nucleated red blood cell count in the umbilical cord (r = 0.46; p<0.01), and a negative correlation with platelet count (r = -0.53; p<0.01) and white blood cell count (r = -0.42; p<0.01). Middle cerebral artery PI was positively correlated with platelet count (r = 0.43; p<0.01) and white blood cell count (r = 0.38; p<0.01), and was negatively correlated with nucleated red blood cell count (r = -0.39; p<0.01). The ductus venosus pulsatility index showed a positive correlation with nucleated red blood cell count (r = 0.36; p<0.01), and a negative correlation with platelet count (r = -0.37; p<0.01) and white blood cell count (r = -0.26; p<0.01). Conclusion. A significant positive or negative correlation between nucleated red blood cell, platelet and white blood cell counts, and Doppler indices suggests an association between placental insufficiency and the fetal hematological response.

Three-dimensional sonographic measurement of contralateral lung volume in fetuses with isolated congenital diaphragmatic hernia

Purpose. To use 3-dimensional sonography (3DUS) to measure contralateral lung volume and evaluate the potential of this measurement to predict neonatal outcome in isolated congenital diaphragmatic hernia (CDH). Methods. Between January 2002 and December 2004, the contralateral lung volumes of 39 fetuses with isolated CDH were measured via 3DUS using rotational multiplanar imaging. The observed/expected contralateral fetal lung volume ratios (o/eContFLVR) were compared with the lung/head ratio (LHR), observed/expected total fetal lung volume ratio (o/e-TotFLVR), and postnatal outcome. Results. Contralateral lung volumes are less reduced than total lung volumes in CDH. The bias and precision of 3DUS in estimating contralateral lung volumes were 0.99 cm(3) and 1.11 cm(3), respectively, with absolute limits of agreement ranging from -1.19 cm(3) to + 3.17 cm(3). The o/e-ContFLVR was significantly lower in neonatal death cases (median, 0.49 cm(3); range, 0.22-0.99 cm(3)) than in survival cases (median, 0.58 cm(3); range, 0.42-0.92 cm(3) [p < 0.011). Overall accuracy of the o/e-ContFLVR, o/e-TotFLVR, and LHR in predicting neonatal death were 67.7% (21/31), 80.7% (25/31), and 77.4% (24/31), respectively. Conclusion. Although o/e-ContFLVR can be precisely measured with 3DUS and can be used to predict neonatal death in CDH, it is less accurate than LHR and o/e-TotFLVR for that purpose. (C) 2007 Wiley Periodicals, Inc.

Time- and Fluid-Sensitive Resuscitation for Hemodynamic Support of Children in Septic Shock Barriers to the Implementation of the American College of Critical Care Medicine/Pediatric Advanced Life Support Guidelines in a Pediatric Intensive Care Unit in a Developing World

Objectives: To analyze mortality rates of children with severe sepsis and septic shock in relation to time-sensitive fluid resuscitation and treatments received and to define barriers to the implementation of the American College of Critical Care Medicine/Pediatric Advanced Life Support guidelines in a pediatric intensive care unit in a developing country. Methods: Retrospective chart review and prospective analysis of septic shock treatment in a pediatric intensive care unit of a tertiary care teaching hospital. Ninety patients with severe sepsis or septic shock admitted between July 2002 and June 2003 were included in this study. Results: Of the 90 patients, 83% had septic shock and 17% had severe sepsis; 80 patients had preexisting severe chronic diseases. Patients with septic shock who received less than a 20-mL/kg dose of resuscitation fluid in the first hour of treatment had a mortality rate of 73%, whereas patients who received more than a 40-mL/kg dose in the first hour of treatment had a mortality rate of 33% (P < 0.05.) Patients treated less than 30 minutes after diagnosis of severe sepsis and septic shock had a significantly lower mortality rate (40%) than patients treated more than 60 Minutes after diagnosis (P < 0.05). Controlling for the risk of mortality, early fluid resuscitation was associated with a 3-fold reduction in the odds of death (odds ratio, 0.33; 95% confidence interval, 0.13-0.85). The most important barriers to achieve adequate severe sepsis and septic shock treatment were lack of adequate vascular access, lack of recognition of early shock, shortage of health care providers, and nonuse of goals and treatment protocols. Conclusions: The mortality rate was higher for children older than years, for those who received less than 40 mL/kg in the first hour, and for those whose treatment was not initiated in the first 30 Minutes after the diagnosis of septic shock. The acknowledgment of existing barriers to a timely fluid administration and the establishment of objectives to overcome these barriers may lead to a more successful implementation of the American College of Critical Care Medicine guidelines and reduced mortality rates for children with septic shock in the developing world.

Association between symptom severity and internal capsule volume in obsessive-compulsive disorder

Neurobiological models support an involvement of white matter tracts in the pathophysiology of obsessive-compulsive disorder (OCD), but there has been little systematic evaluation of white matter volumes in OCD using magnetic resonance imaging (MRI). We investigated potential differences in the volume of the cingulum bundle (CB) and anterior limb of internal capsule (ALIC) in OCD patients (n = 19) relative to asymptomatic control subjects (n = 15). White matter volumes were assessed using a 1.5T MRI scanner. Between-group comparisons were carried out after spatial normalization and image segmentation using optimized voxel-based morphometry. Correlations between regional white matter volumes in OCD subjects and symptom severity ratings were also investigated. We found significant global white matter reductions in OCD patients compared to control subjects. The voxel-based search for regional abnormalities (with covariance for total white matter volumes) showed no specific white matter volume deficits in brain portions predicted a priori to be affected in OCD (CB and ALIC). However, large clusters of significant positive correlation with OCD severity scores were found bilaterally on the ALIC. These findings provide evidence of OCD-related ALIC abnormalities and suggest a connectivity dysfunction within frontal-striatal-thalamic-cortical circuits. Further studies are warranted to better define the role of such white matter alterations in the pathophysiology of OCD, and may provide clues for a more effectively targeting of neurosurgical treatments for OCD. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

The outer wall of small airways is a major site of remodeling in fatal asthma

Background: Structural and inflammatory changes in asthma involve both the large and small airways, with involvement of the distal lung being related to disease severity. We have previously shown that changes in the extracellular matrix (ECM) composition of the distal lung are associated with loss of alveolar attachments in patients with fatal asthma. However, major ECM elements, such as collagen I and fibronectin and their regulators, have not been addressed at the distal level. Objective: We sought to evaluate ECM remodeling in the distal lungs of asthmatic patients. Methods: Using immunohistochemistry and image analysis, we determined the content of collagen I and III, fibronectin, and matrix metalloproteinases; (MMPs) 1, 2, and 9 and tissue inhibitors of metalloproteinase (MMPs) 1 and 2 in the large and small airways and lung parenchyma of 24 patients with fatal asthma and compared the results with those of 11 nonasthmatic control subjects. Protein content was defined as the area of positive staining divided by basement membrane or septum length. Results: We observed increased collagen I and decreased collagen III content in the small airways of asthmatic patients compared with that seen in control subjects. Greater fibronectin and MMP-1, MMP-2, and MMP-9 content was observed at the outer area of the small airways in asthmatic patients. NIMP content was also increased in the peribronchiolar parenchyma in asthmatic patients. In contrast, TIMP expression was only increased in the large airways of asthmatic patients compared with that seen in control subjects. Conclusions: The outer area of the small airways is a major site of ECM remodeling in fatal asthma, potentially contributing to functional changes and the loss of airway-parenchyma interdependence observed in patients with fatal asthma. (J Allergy Clin Immunol 2009;123:1090-7.)

Nodules Less Than 20 mm and Vascular Invasion are Predictors of Survival in Small Hepatocellular Carcinoma

Background: The aims of this study were to analyze the overall survival of patients with cirrhosis and small hepatocellular carcinoma (HCC) and identify independent pretreatment predictors of survival in Brazil. Methods: Between 1998 and 2003, 74 patients with cirrhosis and small HCC were evaluated. Predictors of survival were identified using the Kaplan-Meier survival curves and the Cox model. Results: The overall survival rates were 80%, 41%, and 17% at 12, 36, and 60 months, respectively. The mean length of follow-up after HCC diagnosis was 23 months (median 22 mo, range: I to 86 mo) for the entire group. Univariate analysis showed that model for endstage liver disease (MELD) score (P = 0.016), Child-Pugh classification (P = 0.007), alpha-fetoprotein level (P = 0.006), number of nodules (P = 0.041), tumor diameter (P = 0.009), and vascular invasion (P < 0.0001) were significant predictors Of Survival. Cox regression analysis identified vascular invasion (relative risk = 14.60, confidence interval 95% = 3.3-64.56, P < 0.001) and tumor size > 20 mm (relative risk = 2.14, confidence interval 95% = 1.07-4.2, P = 0.030) as independent predictors of decreased survival. Treatment of HCC was related to increased overall survival. Conclusions: Identification of HCC smaller than 20 mm is associated with longer survival. Presence of vascular invasion, even in small tumors, maybe associated with poor prognosis. Treatment of small tumors Of LIP to 20 mm diameter is related to increased survival.

Small Airway Remodeling in Idiopathic Interstitial Pneumonias: A Pathological Study

Background: Few studies have addressed small airway (SA) histopathological changes and their possible role in the remodeling process in idiopathic interstitial pneumonias. Objectives: To study morphological, morphometrical and immunohistochemical features of SA in idiopathic pulmonary fibrosis (usual interstitial pneumonia, UIP) and nonspecific interstitial pneumonia (NSIP). Methods: We analyzed SA pathology in lung biopsies from 29 patients with UIP and 8 with NSIP. Biopsies were compared with lung tissue from 13 patients with constrictive bronchiolitis (CB) as positive controls and 10 normal autopsied control lungs. We semi-quantitatively analyzed SA structure, inflammation, architectural features and the bronchiolar epithelial immunohistochemical expression of TGF-beta, MMP-2, 7, 9, and their tissue inhibitors (TIMP-1, 2). Results: Compared to controls, patients with UIP, NSIP and CB presented increased bronchiolar inflammation, peribronchiolar inflammation and fibrosis and decreased luminal areas. UIP patients had thicker walls due to an increase in most airway compartments. NSIP patients presented increased epithelial areas, whereas patients with CB had larger inner wall areas. All of the groups studied presented increased bronchiolar expression of MMP-7 and MMP-9, compared to the controls. Conclusion: We conclude that SAs are pathologically altered and may take part in the lung-remodeling process in idiopathic interstitial pneumonias. Copyright (C) 2009 S. Karger AG, Basel

Estimating Investment Risk in Small-Scale Plantation Rainforest Cabinet Timbers and Eucalypts

‘This book is a landmark opening and first attempt at such a process for defining farm forestry, as well as making a contribution to small-scale forestry.’