Hyperacute transplantation of umbilical cord mesenchymal stromal cells in a model of severe intracerebral hemorrhage.

Aim: Intracerebral hemorrhage (ICH) has limited therapeutic options. We have shown that an intravenous injection of human umbilical cord-derived mesenchymal stromal cells (hUC-MSC) 24 h after an ICH in rats reduced the residual hematoma volume after a moderate hemorrhage but was inefficient in severe ICH. Here, we investigated whether a treatment in the hyperacute phase would be more effective in severe ICH. Materials & methods: Wistar rats were randomly selected to receive an intravenous injection of hUC-MSC or the vehicle 1 h after a severe ICH. Results: The hyperacute treatment with hUC-MSC did not affect the 22-day survival rate, the motor function or the residual hematoma volume. Conclusion: These results indicate the need for optimization of hUC-MSC-based therapies for severe ICH.

Semantic verbal fluency brain network: delineating a physiological basis for the functional hubs using dual-echo ASL and graph theory approach.

Objective. Semantic verbal fluency (SFV) is a cognitive process that engages and modulates specific brain areas related to language comprehension and production, decision making, response inhibition, and memory retrieval. The impairment of the brain network responsible for these functions is related to various neurological conditions, and different strategies have been proposed to assess SVF-related deficits in such diseases. In the present study, the concomitant changes of brain perfusion and functional connectivity were investigated during the resting state and SVF task performance.Approach. Arterial spin labeling (ASL), a perfusion-based magnetic resonance imaging (MRI) method, was used with a pseudocontinuous labeling approach and dual-echo readout in 28 healthy right-handed Brazilian Portuguese speakers. The acquisition was performed in a resting state condition and during the performance of a SVF task.Main results. During task performance, a significant increase in cerebral blood flow (CBF) was observed in language-related regions of the frontal lobe, including Brodmann's areas 6, 9, 45, and 47, associated with semantic processing, word retrieval, and speech motor programming. Such regions, along with the posterior cingulate, showed a crucial role in the SVF functional network, assessed by seed-to-voxel and graph analysis. Our approach successfully overcame the generalization problem regarding functional MRI (fMRI) graph analysis with cognitive, task-based paradigms. Moreover, the CBF maps enabled the functional assessment of orbital frontal and temporal regions commonly affected by magnetic susceptibility artifacts in conventional T2*-weighted fMRI approaches.Significance. Our results demonstrated the capability of ASL to evaluate perfusion alterations and functional patterns simultaneously regarding the SVF network providing a quantitative physiological basis to functional hubs in this network, which may support future clinical studies.

Contrast optimization in arterial spin labeling with multiple post-labeling delays for cerebrovascular assessment.

OBJECTIVE: Improving the readout for arterial spin labeling with multiple post-labeling delays (multi-PLD ASL) through a flip angle (FA) sweep towards increasing contrast-to-noise ratio for long PLD images. METHODS: Images were acquired from 20 healthy subjects and 14 patients with severe, asymptomatic carotid artery stenosis (ACAS) in a 3T MRI scanner. Multi-PLD ASL images with conventional and proposed (FA sweep) readouts were acquired. For patients, magnetic resonance angiography was used to validate the multi-PLD ASL results. Perfusion values were calculated for brain regions irrigated by the main cerebral arteries and compared by analysis of variance. RESULTS: For healthy subjects, better contrast was obtained for long PLDs when using the proposed multi-PLD method compared to the conventional. For both methods, no hemispheric difference of perfusion was observed. For patients, the proposed method facilitated the observation of delayed tissue perfusion, which was not visible for long PLD using the conventional multi-PLD ASL. CONCLUSION: We successfully assessed brain perfusion of patients with asymptomatic CAS using multi-PLD ASL with FA sweep. We were able to show subtle individual differences. Moreover, prolonged arterial transit time in patients was observed, although they were considered asymptomatic, suggesting that it may not be an adequate term to characterize them.

Can gadoxetic acid-enhanced magnetic resonance imaging be used to avoid liver biopsy in patients with nonalcoholic fatty liver disease?

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. The diagnosis of nonalcoholic steatohepatitis (NASH), the most severe form of NAFLD, is crucial and has prognostic and therapeutic implications. However, currently this diagnosis is based on liver biopsy and has several limitations. AIM: To evaluate the performance of gadoxetic acid-enhanced magnetic resonance imaging (GA-MRI) in differentiating isolated steatosis from NASH in patients with NAFLD. METHODS: In this prospective study, 56 patients with NAFLD (18 with isolated steatosis and 38 with NASH) underwent GA-MRI. The contrast enhancement index (CEI) was calculated as the rate of increase of the liver-to-muscle signal intensity ratio from before and 20 min after intravenous GA administration. Between-group differences in mean CEI were examined using Student's t test. The area under the receiver operator characteristic curve and the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging were evaluated. RESULTS: The mean CEI for all subjects was 1.82 ± 0.19. The mean CEI was significantly lower in patients with NASH than in those with isolated steatosis (P = 0.008). Two CEI cut-off points were used: < 1.66 (94% specificity) to characterize NASH and > 2.00 (89% sensitivity) to characterize isolated steatosis. CEI values between 1.66 and 2.00 indicated liver biopsy, and the procedure could be avoided in 40% of patients with NAFLD. CONCLUSION: GA-MRI is an effective noninvasive method that may be useful for the differentiation of NASH from isolated steatosis, and could help to avoid liver biopsy in patients with NAFLD.

Higher cut-off values of non-invasive methods might be needed to detect moderate-to-severe steatosis in morbid obese patients: a pilot study.

To evaluate the diagnostic value of described thresholds of controlled attenuation parameter (CAP) and biomarker scores for liver steatosis and to evaluate new cut-offs to detect moderate-to-severe steatosis (S2-3) in patients with morbid obesity. In this prospective study, 32 patients with morbid obesity with indications for bariatric surgery (15 women and 17 men, mean age = 36 years, median BMI = 40.2 kg/m2) underwent CAP, magnetic resonance spectroscopy (MRS), three biomarker scores (Steato-ELSA, Fatty Liver Index (FLI), and Hepatic Steatosis Index (HSI)), and liver biopsy. Subjects were divided into an exploratory cohort (reliable CAP and liver biopsy) and a confirmatory cohort (reliable CAP and MRS) to evaluate new thresholds for CAP and biomarker scores to detect S2-3. Receiver operator characteristic (ROC) curves analyses were performed and the optimal cut-off points were identified using the maximal Youden index. A total of 22 patients had CAP measure and liver biopsy (exploratory cohort) and 24 patients had CAP measure with MRS (confirmatory cohort). New cut-offs were identified for detection of S2-3 by the non-invasive tests using liver biopsy as the reference standard (exploratory cohort). Considering the new proposed cut-offs for detection of S2-3 for CAP (≥ 314 dB/m), Steato-ELSA (≥ 0.832), FLI (≥ 96), and HSI (≥ 53), for the exploratory and confirmatory cohorts sensitivities were: 71-75%, 86-81%, 85-81%, and 71-69% and specificities were: 94-89%, 75-63%, 63-63%, and 75-88%, respectively. Higher cut-offs for CAP and biomarker scores may be better to diagnose moderate-to-severe steatosis in patients with morbid obesity.

Intravenous Human Umbilical Cord-Derived Mesenchymal Stromal Cell Administration in Models of Moderate and Severe Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is as a life-threatening condition that can occur in young adults, often causing long-term disability. Recent preclinical data suggest mesenchymal stromal cell (MSC)-based therapies as promising options to minimize brain damage after ICH. However, therapeutic evidence and mechanistic insights are still limited, particularly when compared with other disorders such as ischemic stroke. Herein, we employed a model of collagenase-induced ICH in young adult rats to investigate the potential therapeutic effects of an intravenous injection of human umbilical cord Wharton's jelly-derived MSCs (hUC-MSCs). Two doses of collagenase were used to cause moderate or severe hemorrhages. Magnetic resonance imaging showed that animals treated with hUC-MSCs after moderate ICH had smaller residual hematoma volumes than vehicle-treated rats, whereas the cell therapy failed to decrease the hematoma volume in animals with a severe ICH. Functional assessments (rotarod and elevated body swing tests) were performed for up to 21 days after ICH. Enduring neurological impairments were seen only in animals subjected to severe ICH, but the cell therapy did not induce statistically significant improvements in the functional recovery. The biodistribution of Technetium-99m-labeled hUC-MSCs was also evaluated, showing that most cells were found in organs such as the spleen and lungs 24 h after transplantation. Nevertheless, it was possible to detect a weak signal in the brain, which was higher in the ipsilateral hemisphere of rats subjected to a severe ICH. These data indicate that hUC-MSCs have moderately beneficial effects in cases of less severe brain hemorrhages in rats by decreasing the residual hematoma volume, and that optimization of the therapy is still necessary.

Preperitoneal fat as a non-invasive marker of increased risk of severe non-alcoholic fatty liver disease in patients with type 2 diabetes.

BACKGROUND AND AIM: Fat distribution may have prognostic value in the evaluation of non-alcoholic fatty liver disease. This study was conducted to evaluate associations of magnetic resonance imaging-measured abdominal fat areas with steatosis, steatohepatitis, and fibrosis, assessed histopathologically, in patients with type 2 diabetes. METHODS: This prospective study included 66 patients with type 2 diabetes (12 males, 54 females, age 26-68 years), without chronic liver disease of other causes. Axial dual-echo magnetic resonance images were acquired. Visceral, subcutaneous, and preperitoneal fat areas were measured using Osirix software. Liver biopsy specimens were obtained from all patients and examined histopathologically to evaluate steatosis, steatohepatitis, and fibrosis. Linear (for steatosis) and logistic (for steatohepatitis and fibrosis) regression models were fitted for the outcomes. R2 was used as a measure of how much model variance the predictors explained and to compare different predictors of the same outcome. RESULTS: Visceral and preperitoneal fat areas correlated well with histopathologically determined liver steatosis grade (both P = 0.004) and liver fibrosis (P = 0.008 and P = 0.037, respectively). All fat areas correlated well with steatohepatitis (P ≤ 0.002). Preperitoneal and visceral fat areas were the best predictors of steatohepatitis (R2 = 0.379) and fibrosis (R2 = 0.181), respectively. CONCLUSIONS: Visceral fat area was the best predictor of fibrosis in patients with type 2 diabetes. Preperitoneal fat area was the best predictor of steatohepatitis and is a potential new non-invasive marker for use in the screening of these patients to detect more aggressive forms of non-alcoholic fatty liver disease.

Manganese-Enhanced MRI: Biological Applications in Neuroscience.

Magnetic resonance imaging (MRI) is an excellent non-invasive tool to investigate biological systems. The administration of the paramagnetic divalent ion manganese (Mn(2+)) enhances MRI contrast in vivo. Due to similarities between Mn(2+) and calcium (Ca(2+)), the premise of manganese-enhanced MRI (MEMRI) is that the former may enter neurons and other excitable cells through voltage-gated Ca(2+) channels. As such, MEMRI has been used to trace neuronal pathways, define morphological boundaries, and study connectivity in morphological and functional imaging studies. In this article, we provide a brief overview of MEMRI and discuss recently published data to illustrate the usefulness of this method, particularly in animal models.

Intravoxel Incoherent Motion Diffusion Weighted MR Imaging at 3.0 T: Assessment of Steatohepatitis and Fibrosis Compared with Liver Biopsy in Type 2 Diabetic Patients.

OBJECTIVE: To evaluate the capability of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) to assess steatohepatitis and fibrosis determined by histopathology in type 2 diabetic patients. METHODS: Fifty-nine type 2 diabetic patients (49 women, 10 men; mean age, 54 ± 9 years) were submitted to liver biopsy for the evaluation of non-alcoholic fatty liver disease (NAFLD) and underwent DWI on a 3.0T MR system using 10 b values. Institutional approval and patient consent were obtained. Pure molecular-based (D), perfusion-related (D*), and vascular fraction (f) were calculated using a double exponential model and least squares curve fitting. D, D*, and f were compared between patients with and without steatohepatitis and between patients with and without fibrosis. The variables were compared by using the Ranksum test and Student t-test. RESULTS: Steatohepatitis was observed in 22 patients and fibrosis in 16 patients. A lower D median (0.70 s/mm2 vs. 0.83 s/mm2, p<0.05) and a lower D* median (34.39 s/mm2 vs. 45.23 s/mm2, p<0.05) were observed among those with steatohepatitis. A lower D median (0.70 s/mm2 vs. 0.82 s/mm2, p<0.05) and a lower D* median (35.01 s/mm2 vs. 44.76 s/mm2, p=0.05) were also observed among those with fibrosis. CONCLUSION: IVIM-DWI has the potential to aid in the characterization of steatohepatitis and fibrosis.

Is MR spectroscopy really the best MR-based method for the evaluation of fatty liver in diabetic patients in clinical practice?

OBJECTIVE: To investigate if magnetic resonance spectroscopy (MRS) is the best Magnetic Resonance (MR)-based method when compared to gradient-echo magnetic resonance imaging (MRI) for the detection and quantification of liver steatosis in diabetic patients in the clinical practice using liver biopsy as the reference standard, and to assess the influence of steatohepatitis and fibrosis on liver fat quantification. METHODS: Institutional approval and patient consent were obtained for this prospective study. Seventy-three patients with type 2 diabetes (60 women and 13 men; mean age, 54 ± 9 years) underwent MRI and MRS at 3.0 T. The liver fat fraction was calculated from triple- and multi-echo gradient-echo sequences, and MRS data. Liver specimens were obtained in all patients. The accuracy for liver fat detection was estimated by receiver operator characteristic (ROC) analysis, and the correlation between fat quantification by imaging and histolopathology was analyzed by Spearman's correlation coefficients. RESULTS: The prevalence of hepatic steatosis was 92%. All gradient-echo MRI and MRS findings strongly correlated with biopsy findings (triple-echo, rho = 0.819; multi-echo, rho = 0.773; MRS, rho = 0.767). Areas under the ROC curves to detect mild, moderate, and severe steatosis were: triple-echo sequences, 0.961, 0.975, and 0.962; multi-echo sequences, 0.878, 0.979, and 0.961; and MRS, 0.981, 0.980, and 0.954. The thresholds for mild, moderate, and severe steatosis were: triple-echo sequences, 4.09, 9.34, and 12.34, multi-echo sequences, 7.53, 11.75, and 15.08, and MRS, 1.71, 11.69, and 14.91. Quantification was not significantly influenced by steatohepatitis or fibrosis. CONCLUSIONS: Liver fat quantification by MR methods strongly correlates with histopathology. Due to the wide availability and easier post-processing, gradient-echo sequences may represent the best imaging method for the detection and quantification of liver fat fraction in diabetic patients in the clinical practice.

Comparison of human brain metabolite levels using 1H MRS at 1. 5T and 3. 0T / Comparação dos níveis de metabólitos cerebrais utilizando espectroscopia de prótons por ressonância magnética em 1. 5T e 3. 0T

Proton magnetic resonance spectroscopy (MRS) of the human brain has proven to be a useful technique in several neurological and psychiatric disorders and benefits from higher scanners as signal intensity and spectral resolution are proportional to the magnetic strength. OBJECTIVE: To investigate the effects of the magnetic on the measurement of brain metabolites in a typical routine clinical setting. METHODS: Single voxel spectra were acquired from the posterior cingulate cortex in 26 healthy subjects. Each subject was scanned consecutively at 1.5T and 3.0T in a randomly distributed order. RESULTS: SNR and peak width improvements were observed at higher s. However, SNR improvement was lower than the theoretical two-fold improvement. Other than the values obtained for creatine (Cre) and myo-Inositol (mI), which were both higher at 3.0T, all metabolite concentrations obtained were roughly the same at both strengths. All the metabolite concentrations were estimated with a Cramer Rao lower bounds (CRLB) lower than 15% of the calculated concentrations. CONCLUSIONS: Even though the present study supports the expected benefits of higher strength for MRS, there are several factors that can lead to different quantitative results when comparing 1.5T to 3.0T MRS. Future comparative studies are necessary to refine the metabolite thresholds for early detection and quantification of distinct neurological and psychiatric disorders using 3.0T MRS.

Espectroscopia de prótons por ressonância magnética (MRS) tem se mostrado uma técnica bastante útil em diversas doenças neurológicas e psiquiátricas. A utilização de sistemas de mais alto campo magnético favorece essa técnica uma vez que a intensidade do sinal e a resolução espectral são proporcionais à intensidade do campo. OBJETIVO: Avaliar o efeito do campo magnético sobre a medida dos níveis dos metabólitos cerebrais em uma típica rotina clínica. MÉTODOS: Os dados foram obtidos em 26 indivíduos saudáveis nos sistemas de 1.5T e 3.0T. As aquisições foram feitas sequencialmente e a ordem foi distribuida randomicamente.RESULTADOS: Foram observadas melhoras na relação sinal-ruído (SNR) e na largura de linha dos picos nos dados obtidos em campo maior. No entanto, a melhoria na SNR foi menor que o esperado teoricamente que seria o dobro da obtida em 1.5T. Exceto pelos valores obtidos para creatina e mio-inositol, que foram maiores em 3.0T, todas as concentrações de metabólitos obtidas foram aproximadamente a mesmo em ambos os campos. Todas as concentrações de metabólitos foram estimadas com Cramer Rao lower bounds (CRLB) inferior a 15% das concentrações calculadas. CONCLUSÕES: Apesar de o presente estudo dar suporte aos benefícios gerados pelo aumento do campo para a técnica de MRS, existem fatores que podem levar a diferentes resultados quantitativos quando se compara espectroscopia em 1.5T e 3.0T. Estudos comparativos serão necessários para refinar os limiares dos níveis de metabólitos para melhorar a acurácia da detecção de doenças neurológicas utilizando espectroscopia em 3.0T.

Comparison of human brain metabolite levels using 1H MRS at 1.5T and 3.0T.

Proton magnetic resonance spectroscopy (MRS) of the human brain has proven to be a useful technique in several neurological and psychiatric disorders and benefits from higher field scanners as signal intensity and spectral resolution are proportional to the magnetic field strength. OBJECTIVE: To investigate the effects of the magnetic field on the measurement of brain metabolites in a typical routine clinical setting. METHODS: Single voxel spectra were acquired from the posterior cingulate cortex in 26 healthy subjects. Each subject was scanned consecutively at 1.5T and 3.0T in a randomly distributed order. RESULTS: SNR and peak width improvements were observed at higher fields. However, SNR improvement was lower than the theoretical two-fold improvement. Other than the values obtained for creatine (Cre) and myo-Inositol (mI), which were both higher at 3.0T, all metabolite concentrations obtained were roughly the same at both field strengths. All the metabolite concentrations were estimated with a Cramer Rao lower bounds (CRLB) lower than 15% of the calculated concentrations. CONCLUSIONS: Even though the present study supports the expected benefits of higher field strength for MRS, there are several factors that can lead to different quantitative results when comparing 1.5T to 3.0T MRS. Future comparative studies are necessary to refine the metabolite thresholds for early detection and quantification of distinct neurological and psychiatric disorders using 3.0T MRS.

Espectroscopia de prótons por ressonância magnética (MRS) tem se mostrado uma técnica bastante útil em diversas doenças neurológicas e psiquiátricas. A utilização de sistemas de mais alto campo magnético favorece essa técnica uma vez que a intensidade do sinal e a resolução espectral são proporcionais à intensidade do campo. OBJETIVO: Avaliar o efeito do campo magnético sobre a medida dos níveis dos metabólitos cerebrais em uma típica rotina clínica. MÉTODOS: Os dados foram obtidos em 26 indivíduos saudáveis nos sistemas de 1.5T e 3.0T. As aquisições foram feitas sequencialmente e a ordem foi distribuida randomicamente. RESULTADOS: Foram observadas melhoras na relação sinal-ruído (SNR) e na largura de linha dos picos nos dados obtidos em campo maior. No entanto, a melhoria na SNR foi menor que o esperado teoricamente que seria o dobro da obtida em 1.5T. Exceto pelos valores obtidos para creatina e mio-inositol, que foram maiores em 3.0T, todas as concentrações de metabólitos obtidas foram aproximadamente a mesmo em ambos os campos. Todas as concentrações de metabólitos foram estimadas com Cramer Rao lower bounds (CRLB) inferior a 15% das concentrações calculadas. CONCLUSÕES: Apesar de o presente estudo dar suporte aos benefícios gerados pelo aumento do campo para a técnica de MRS, existem fatores que podem levar a diferentes resultados quantitativos quando se compara espectroscopia em 1.5T e 3.0T. Estudos comparativos serão necessários para refinar os limiares dos níveis de metabólitos para melhorar a acurácia da detecção de doenças neurológicas utilizando espectroscopia em 3.0T.