Josep Puig

Instituto de Salud Carlos III, Madrid, Madrid, Spain

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Publications (46)140.04 Total impact

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    ABSTRACT: Lesion detection in acute stroke by computed-tomography perfusion (CTP) can be affected by incomplete bolus coverage in veins and hypoperfused tissue, so-called bolus truncation (BT), and low contrast-to-noise ratio (CNR). We examined the BT-frequency and hypothesized that image down-sampling and a vascular model (VM) for perfusion calculation would improve normo- and hypoperfused tissue classification. CTP datasets from 40 acute stroke patients were retrospectively analysed for BT. In 16 patients with hypoperfused tissue but no BT, repeated 2-by-2 image down-sampling and uniform filtering was performed, comparing CNR to perfusion-MRI levels and tissue classification to that of unprocessed data. By simulating reduced scan duration, the minimum scan-duration at which estimated lesion volumes came within 10 % of their true volume was compared for VM and state-of-the-art algorithms. BT in veins and hypoperfused tissue was observed in 9/40 (22.5 %) and 17/40 patients (42.5 %), respectively. Down-sampling to 128 × 128 resolution yielded CNR comparable to MR data and improved tissue classification (p = 0.0069). VM reduced minimum scan duration, providing reliable maps of cerebral blood flow and mean transit time: 5 s (p = 0.03) and 7 s (p < 0.0001), respectively). BT is not uncommon in stroke CTP with 40-s scan duration. Applying image down-sampling and VM improve tissue classification. • Too-short imaging duration is common in clinical acute stroke CTP imaging. • The consequence is impaired identification of hypoperfused tissue in acute stroke patients. • The vascular model is less sensitive than current algorithms to imaging duration. • Noise reduction by image down-sampling improves identification of hypoperfused tissue by CTP.
    European Radiology 04/2015; DOI:10.1007/s00330-015-3602-x · 4.34 Impact Factor
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    ABSTRACT: Objective Whether nonalcoholic fatty liver disease (NAFLD) can predict atherosclerosis in obese patients remains unclear. The aim of our study was to investigate the usefulness of NAFLD and other cardiometabolic parameters in predicting subclinical atherosclerosis in obese patients.Design, Patients and MeasurementsWe studied 314 consecutive obese subjects (223 women; mean age, 45.04±9.34 years; body mass index 44.3±5 Kg/m2) and 47 healthy lean individuals. Hepatic steatosis and atherosclerosis (carotid intima-media thickness [cIMT]>0.8 mm and/or presence of plaques) were evaluated ultrasonographically. Liver biopsies were obtained in 51 patients.ResultsIn obese patients, mean c-IMT was greater in those with NAFLD (P<0.001). Hepatic steatosis and age were independent predictors of atherosclerosis: the NAFLD-associated OR for atherosclerosis was 5.96 (95%CI, 1.60-22.25;p=0.008) in men and 8.26 (95%CI, 4.02-16.99;p<0.001) in women, and the age-associated OR for atherosclerosis was 1.14 (95%CI, 1.07-1.22; p<0.001) in men and 1.12 (95%CI, 1.08-1.17; p<0.001) in women. The sensitivity, specificity, and positive and negative predictive values of steatosis for atherosclerosis were 78.70%, 70.50%, 74.00%, and 75.60% (AUC=0.840) in men ≥43.5 years and 86.90%, 52.50%, 68.80%, and 76.80% (AUC=0.761) in women ≥47.5 years, respectively. Agreement between ultrasound-diagnosed steatosis and histology was good (ICC=0.79). Combined NAFLD and age was the strongest predictor of atherosclerosis in obesity.ConclusionsNAFLD and age may be independent risk factors for carotid atherosclerosis in obese individuals. Obese men and women with steatosis aged over 43.5 and 47.5 years, respectively, should be screened for carotid atherosclerosis. However, further evidence is necessary before suggesting an intervention based on current findings.This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 12/2014; DOI:10.1111/cen.12698 · 3.35 Impact Factor
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    ABSTRACT: Arterial pulse wave velocity (PWV), an independent predictor of cardiovascular disease, physiologically increases with age; however, growing evidence suggests metabolic syndrome (MetS) accelerates this increase. Magnetic resonance imaging (MRI) enables reliable noninvasive assessment of arterial stiffness by measuring arterial PWV in specific vascular segments. We investigated the association between the presence of MetS and its components with carotid PWV (cPWV) in asymptomatic subjects without diabetes. We assessed cPWV by MRI in 61 individuals (mean age, 55.3 ± 14.1 years; median age, 55 years): 30 with MetS and 31 controls with similar age, sex, body mass index, and LDL-cholesterol levels. The study population was dichotomized by the median age. To remove the physiological association between PWV and age, unpaired t tests and multiple regression analyses were performed using the residuals of the regression between PWV and age. cPWV was higher in middle-aged subjects with MetS than in those without (p = 0.001), but no differences were found in elder subjects (p = 0.313). cPWV was associated with diastolic blood pressure (r = 0.276, p = 0.033) and waist circumference (r = 0.268, p = 0.038). The presence of MetS was associated with increased cPWV regardless of age, sex, blood pressure, and waist (p = 0.007). The MetS components contributing independently to an increased cPWV were hypertension (p = 0.018) and hypertriglyceridemia (p = 0.002). The presence of MetS is associated with an increased cPWV in middle-aged subjects. In particular, hypertension and hypertriglyceridemia may contribute to early progression of carotid stiffness.
    The International Journal of Cardiovascular Imaging 11/2014; 31(3). DOI:10.1007/s10554-014-0578-6 · 2.32 Impact Factor
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    ABSTRACT: Context: Growing evidence implicates hypothalamic inflammation in the pathogenesis of diet-induced obesity and cognitive dysfunction in rodent models. Few studies have addressed the association between obesity and hypothalamic damage in humans and its relevance. Objective: To determine markers of obesity-associated hypothalamic damage on diffusion tensor imaging (DTI) and to determine whether DTI-metrics are associated with performance on cognitive testing. Design and Participants: This cross-sectional study analyzed DTI-metrics (primary (λ1), secondary (λ2), and tertiary (λ3) eigenvalues; fractional anisotropy (FA); and mean diffusivity (MD)) in the hypothalamus of 24 consecutive middle-aged obese subjects (13 women; 49.8 ± 8.1 years; body mass index [BMI] 43.9 ± 0.92 Kg/m(2)) and 20 healthy volunteers (10 women; 48.8 ± 9.5 years; BMI 24.3 ± 0.79 Kg/m(2)). Outcome: measures: Hypothalamic damage assessed by DTI-metrics and cognitive performance evaluated by neuropsychological test-battery. Results: λ1 values in the hypothalamus were significantly lower in obese subjects (P<0.0001). The sensitivity, specificity, and positive and negative predictive values for obesity-associated hypothalamic damage by λ1<1.072 were 75%, 87.5%, 83.3%, and 80.7%, respectively. Patients with hypothalamic λ1<1.072 had higher values of BMI, fat mass, inflammatory markers, carotid-intima media thickness, and hepatic steatosis and lower scores on cognitive tests. Combined BMI and alanine aminotransferase had the strongest association with hypothalamic damage reflected by λ1<1.072 (AUC=0.89). Conclusions: DTI detects obesity-associated hypothalamic damage associated with inflammatory markers and worse cognitive performance. This study highlights the potential utility of λ1 as a surrogate marker of obesity-associated hypothalamic damage.
    Journal of Clinical Endocrinology &amp Metabolism 11/2014; 100(2):jc20142682. DOI:10.1210/jc.2014-2682 · 6.31 Impact Factor
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    ABSTRACT: OBJECTIVE The linkage among the tissue iron stores, insulin resistance (IR), and cognition remains unclear in the obese population. We aimed to identify the factors that contribute to increased hepatic iron concentration (HIC) and brain iron overload (BIO), as evaluated by MRI, and to evaluate their impact on cognitive performance in obese and nonobese subjects. RESEARCH DESIGN AND METHODS We prospectively recruited 23 middle-aged obese subjects without diabetes (13 women; age 50.4 +/- 7.7 years; BMI 43.7 +/- 4.48 kg/m(2)) and 20 healthy nonobese volunteers (10 women; age 48.8 +/- 9.5 years; BMI 24.3 +/- 3.54 kg/m(2)) inwhomiron load was assessed in white and gray matter and the liver by MRI. IR was measured from HOMA-IR and an oral glucose tolerance test. A battery of neuropsychological tests was used to evaluate the cognitive performance. Multivariate regression analysis was used to identify the independent associations of BIO and cognitive performance. RESULTS A significant increase in iron load was detected at the caudate nucleus (P < 0.001), lenticular nucleus (P = 0.004), hypothalamus (P = 0.002), hippocampus (P < 0.001), and liver (P < 0.001) in obese subjects. There was a positive correlation between HIC and BIO at caudate (r = 0.517, P < 0.001), hypothalamus (r = 0.396, P = 0.009), and hippocampus (r = 0.347, P < 0.023). The area under the curve of insulin was independently associated with BIO at the caudate (P = 0.001), hippocampus (P = 0.028), and HIC (P = 0.025). BIOs at the caudate (P = 0.028), hypothalamus (P = 0.006), and lenticular nucleus (P = 0.012) were independently associated with worse cognitive performance. CONCLUSIONS Obesity and IR may contribute to increased HIC and BIO being associated with worse cognitive performance. BIO could be a potentially useful MRI biomarker for IR and obesity-associated cognitive dysfunction.
    Diabetes Care 08/2014; 37(11). DOI:10.2337/dc14-0664 · 8.57 Impact Factor
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    ABSTRACT: Mast cells participate in atherogenesis by releasing cytokines to induce vascular cell protease expression. Tryptase is expressed highly in human atherosclerotic lesions and the inhibition of tryptase activity hampers its capacity to maintain cholesterol inside macrophague foam cells. We aimed to investigate the association between circulating tryptase levels and subclinical atherosclerosis through estimation of carotid intima-media thickness (c-IMT) as surrogate marker for increased cardiovascular risk in obese and non-obese subjects. Circulating tryptase levels (ELISA) and metabolic parameters were analyzed in 228 subjects. Atherosclerosis (c-IMT>0.9 mm) was evaluated ultrasonographically. Significant positive associations were evident between circulating tryptase levels and BMI, fat mass, glycated haemoglobin, fasting insulin, HOMAIR, fasting triglycerides and ultrasensitive PCR (p<0.05 from linear-trend ANOVA). The positive association between tryptase levels and insulin resistance parameters, suggested a glucose homeostasis impairment in individuals with higher tryptase levels. The negative asociation between tryptase levels and HDL-cholesterol supports the proatherogenic role of this protease (p<0.0001). Circulating tryptase levels were strongly associated with c-IMT measurements (p<0.0001 from linear-trend ANOVA), and were higher in subjects with presence of carotid plaque (p<0.0001). Tryptase levels (beta = 0.015, p = 0.001) contributed independently to subclinical atherosclerosis variance after controlling for cardiovascular risk factors (BMI, blood pressure, LDL-cholesterol). Circulating tryptase level is associated to obesity related parameters and has a close relation with various metabolic risk factors. Moreover, serum tryptase level was independently associated with c-IMT, suggesting its potential use as a surrogate marker for subclinical atherosclerosis in obese subjects.
    PLoS ONE 05/2014; 9(5):e97014. DOI:10.1371/journal.pone.0097014 · 3.53 Impact Factor
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    ABSTRACT: In the early days after ischemic stroke, information on structural brain damage from MRI supports prognosis of functional outcome. It is rated widely by the modified Rankin Scale that correlates only moderately with lesion volume. We therefore aimed to elucidate the influence of lesion location from early MRI (days 2-3) on functional outcome after 1 month using voxel-based lesion symptom mapping. We analyzed clinical and MRI data of patients from a prospective European multicenter stroke imaging study (I-KNOW). Lesions were delineated on fluid-attenuated inversion recovery images on days 2 to 3 after stroke onset. We generated statistic maps of lesion contribution related to clinical outcome (modified Rankin Scale) after 1 month using voxel-based lesion symptom mapping. Lesion maps of 101 patients with middle cerebral artery infarctions were included for analysis (right-sided stroke, 47%). Mean age was 67 years, median admission National Institutes of Health Stroke Scale was 11. Mean infarct volumes were comparable between both sides (left, 37.5 mL; right, 43.7 mL). Voxel-based lesion symptom mapping revealed areas with high influence on higher modified Rankin Scale in regions involving the corona radiata, internal capsule, and insula. In addition, asymmetrically distributed impact patterns were found involving the right inferior temporal gyrus and left superior temporal gyrus. In this group of patients with stroke, characteristic lesion patterns in areas of motor control and areas involved in lateralized brain functions on early MRI were found to influence functional outcome. Our data provide a novel map of the impact of lesion localization on functional stroke outcome as measured by the modified Rankin Scale.
    Stroke 04/2014; 45(6). DOI:10.1161/STROKEAHA.114.005152 · 6.02 Impact Factor
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    ABSTRACT: WAKE-UP is a randomized, placebo-controlled MRI-based trial of thrombolysis in wake-up stroke using the mismatch between a lesion's visibility in diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) sequences as its main imaging inclusion criterion. Visual judgment of lesion conspicuity on FLAIR is however methodically limited by moderate inter-rater agreement. We therefore sought to improve rating homogeneity by incorporating quantitative signal intensity measurements. One hundred forty-three data sets of patients with acute ischemic stroke were visually rated by 8 raters with respect to WAKE-UP study inclusion and exclusion criteria, and inter-rater agreement was calculated. A subanalysis was performed on 45 cases to determine a threshold value of relative signal intensity (rSI) between the ischemic lesion and contralateral healthy tissue which best corresponded to a visually established verdict of FLAIR positivity. The usefulness of this threshold in improving inter-rater agreement was evaluated in an additional sample of 50 patients. Inter-rater agreement for inclusion into the WAKE-UP trial was 73% with a free-marginal κ of 0.46. A threshold of rSI which best correlated with the visual rating of lesions as FLAIR positive was 1.20. The addition of rSI measurements to visual evaluation did not change the inter-rater agreement. Introducing a semiquantitative measure for FLAIR rSI did not improve the agreement between individual raters. However, enhancing visual assessment with rSI measurements can provide reassurance to local investigators in cases of uncertainty.
    Stroke 02/2014; 45(4). DOI:10.1161/STROKEAHA.113.002661 · 6.02 Impact Factor
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    ABSTRACT: Recently, serum lipopolysaccharide-binding protein (LBP) has been closely associated with coronary artery disease. Here, we aimed to investigate the possible relationship between serum LBP and markers of atherosclerosis. Serum LBP and carotid intima media thickness (C-IMT) were measured in 332 subjects (101 men and 231 women) who were recruited from an ongoing multicenter project. Serum LBP was significantly associated with obesity [BMI, fat mass and waist circumference (r > 0.38, p < 0.0001)], HOMA (r = 0.36, p < 0.0001) and high sensitivity CRP (hsCRP) (r = 0.50, p < 0.0001). Circulating LBP was also positively associated with C-IMT (r = 0.27, p < 0.0001). Circulating LBP (β = 0.16; p = 0.001) contributed independently to C-IMT variance, after controlling for the effects of age, gender, BMI and hsCRP. Of note, circulating LBP was found to be increased in the population with carotid plaque (n = 50; 32.7 ± 12.5 vs 28.7 ± 10.7; p = 0.021). The consistent association between serum LBP and the carotid intima media thickness, a widely used atherosclerosis marker, reveals serum LBP as a putative factor related to atherosclerosis.
    Atherosclerosis 10/2013; 230(2):223-7. DOI:10.1016/j.atherosclerosis.2013.07.004 · 3.97 Impact Factor
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    ABSTRACT: Cerebral hypoperfusion induced by bilateral common carotid artery occlusion (BCCAo) in rodents has been proposed as an experimental model of white matter damage and vascular dementia. However, the histopathological and behavioral alterations reported in this model are variable and a full characterization of the dynamic alterations is not available. Here we implemented a longitudinal multimodal magnetic resonance imaging (MRI) design, including time-of-flight angiography, high resolution T1-weighted images, T2 relaxometry mapping, diffusion tensor imaging, and cerebral blood flow measurements up to 12 weeks after BCCAo or sham-operation in Wistar rats. Changes in MRI were related to behavioral performance in executive function tasks and histopathological alterations in the same animals. MRI frequently (70%) showed various degrees of acute ischemic lesions, ranging from very small to large subcortical infarctions. Independently, delayed MRI changes were also apparent. The patterns of MRI alterations were related to either ischemic necrosis or gliosis. Progressive microstructural changes revealed by diffusion tensor imaging in white matter were confirmed by observation of myelinated fiber degeneration, including severe optic tract degeneration. The latter interfered with the visually cued learning paradigms used to test executive functions. Independently of brain damage, BCCAo induced progressive arteriogenesis in the vertebrobasilar tree, a process that was associated with blood flow recovery after 12 weeks. The structural alterations found in the basilar artery were compatible with compensatory adaptive changes driven by shear stress. In summary, BCCAo in rats induces specific signatures in multimodal MRI that are compatible with various types of histological lesion and with marked adaptive arteriogenesis.
    PLoS ONE 09/2013; 8(9):e74631. DOI:10.1371/journal.pone.0074631 · 3.53 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Nearly 50% of patients have residual motor deficits after stroke, and long-term motor outcome is difficult to predict. We assessed the predictive value of axonal damage to the corticospinal tract indexed by diffusion tensor imaging fractional anisotropy for long-term motor outcome. METHODS: Consecutive patients with middle cerebral artery stroke underwent multimodal MRI, including diffusion tensor imaging ≤12 hours, 3 days, and 30 days after onset. Clinical severity, infarct volume, location of corticospinal tract damage on diffusion tensor tractography, and ratios of fractional anisotropy (rFA) between affected and unaffected sides of the corticospinal tract at the pons were evaluated. Severity of motor deficit at 2 years was categorized using the Motricity Index as no deficit (Motricity Index, 100), slight-moderate deficit (Motricity Index, 99-50), or severe deficit (Motricity Index, <50). RESULTS: We evaluated 70 patients (28 women; 72±12 years). rFA values at day 30 correlated with the degree of motor deficit at 2 years (P<0.001). rFA at day 30 was the only independent predictor of long-term motor outcome (odds ratio, 1.60; 95% confidence interval, 1.26-2.03; P<0.001). The sensitivity, specificity, and positive and negative predictive values of the cutoffs rFA<0.982 for predicting slight-moderate deficit and rFA<0.689 for severe deficit were 94.4%, 84.6%, 73.9%, and 97.1%, respectively, and 100%, 83.3%, 81.3%, and 100%, respectively. CONCLUSIONS: rFA at day 30 is an independent predictor of long-term motor outcome after stroke.
    Stroke 05/2013; 44(7). DOI:10.1161/STROKEAHA.111.000382 · 6.02 Impact Factor
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    ABSTRACT: Fibroblast growth factor 23 (FGF-23) is known to be produced by the bone and linked to metabolic risk. We aimed to explore circulating FGF-23 in association with fatness and insulin sensitivity, atherosclerosis and bone mineral density (BMD). Circulating intact FGF-23 (iFGF-23) and C-terminal (CtFGF-23) concentrations (ELISA) were measured in 133 middle aged men from the general population in association with insulin sensitivity (Cohort 1); and in association with fat mass and bone mineral density (DEXA) and atherosclerosis (intima media thickness, IMT) in 78 subjects (52 women) with a wide range of adiposity (Cohort 2). Circulating iFGF-23 was also measured before and after weight loss. In all subjects as a whole, serum intact and C-terminal concentrations were linearly and positively associated with BMI. In cohort 1, both serum iFGF-23 and CtFGF-23 concentrations increased with insulin resistance. Serum creatinine contributed to iFGF-23 variance, while serum ferritin and insulin sensitivity (but not BMI, age or serum creatinine) contributed to 17% of CtFGF-23 variance. In cohort 2, CtFGF-23 levels were higher in women vs. men, and increased with BMI, fat mass, fasting and post-load serum glucose, insulin, HOMA-IR and PTH, being negatively associated with circulating vitamin D and ferritin levels. The associations of CtFGF-23 with bone density in the radius, lumbar spine and carotid IMT were no longer significant after controlling for BMI. Weight loss led to decreased iFGF-23 concentrations. In summary, the associations of circulating FGF-23 concentration with parameters of glucose metabolism, bone density and atherosclerosis are dependent on iron and obesity status-associated insulin resistance.
    PLoS ONE 03/2013; 8(3):e58961. DOI:10.1371/journal.pone.0058961 · 3.53 Impact Factor
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    ABSTRACT: RATIONALE: In about 20% of acute ischemic stroke patients stroke occurs during sleep. These patients are generally excluded from intravenous thrombolysis. MRI can identify patients within the time-window for thrombolysis (≤4·5 h from symptom onset) by a mismatch between the acute ischemic lesion visible on diffusion weighted imaging (DWI) but not visible on fluid-attenuated inversion recovery (FLAIR) imaging. AIMS AND HYPOTHESIS: The study aims to test the efficacy and safety of MRI-guided thrombolysis with tissue plasminogen activator (rtPA) in ischemic stroke patients with unknown time of symptom onset, e.g., waking up with stroke symptoms. We hypothesize that stroke patients with unknown time of symptom onset with a DWI-FLAIR-mismatch pattern on MRI will have improved outcome when treated with rtPA compared to placebo. DESIGN: WAKE-UP is an investigator initiated, European, multicentre, randomized, double-blind, placebo-controlled clinical trial. Patients with unknown time of symptom onset who fulfil clinical inclusion criteria (disabling neurological deficit, no contraindications against thrombolysis) will be studied by MRI. Patients with MRI findings of a DWI-FLAIR-mismatch will be randomised to either treatment with rtPA or placebo. STUDY OUTCOME: The primary efficacy endpoint will be favourable outcome defined by modified Rankin Scale 0-1 at day 90. The primary safety outcome measures will be mortality and death or dependency defined by modified Rankin Scale 4-6 at 90 days. DISCUSSION: If positive, WAKE-UP is expected to change clinical practice making effective and safe treatment available for a large group of acute stroke patients currently excluded from specific acute therapy.
    International Journal of Stroke 03/2013; 9(6). DOI:10.1111/ijs.12011 · 4.03 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: The role of diffusion tensor imaging in determining stroke age remains unclear. We tested the ability of diffusion tensor imaging metrics to discriminate ischemic stroke <4.5 hours of onset. METHODS: We enrolled 60 consecutive patients for multimodal 1.5 T MRI within 12 hours of middle cerebral artery ischemic stroke onset. We measured fractional anisotropy (FA), mean diffusivity (MD), apparent diffusion coefficient (ADC), and T2-weighted signal intensity in affected ipsilateral and unaffected contralateral deep gray matter, cortical gray matter, deep white matter in the corticospinal tract (CST), and subcortical white matter and calculated ipsilateral-to-contralateral ratios (r). Hyperintensity in infarcted tissue was considered fluid-attenuated inversion recovery-positive. RESULTS: We analyzed the 48 patients (17 women; mean age, 68±14 years) with known onset. In 25 (52.1%) patients, onset was ≤4.5 hours (mean, 182.3±65.6 minutes). Variables differing significantly between infarcts <4.5 hours and >4.5 hours were rFA CST (P=0.001), rMD cortical gray matter (P=0.036), rADC cortical gray matter (P=0.009), rT2 CST (P=0.006), and fluid-attenuated inversion recovery (P<0.001). rFA at CST was the most reliable to discriminate infarcts <4.5 hours (Goodman-Kruskal=0.76). The sensitivity, specificity, and positive and negative predictive values for infarct <4.5 hours of onset by rFA at CST >0.970 were 93.8%, 84.6%, 88.2%, and 91.7%, respectively. CONCLUSIONS: These preliminary results suggest rFA at CST may be a surrogate marker of acute stroke age.
    Stroke 03/2013; 44(4). DOI:10.1161/STROKEAHA.111.678110 · 6.02 Impact Factor
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    ABSTRACT: The pathophysiology of cerebral ischemia is traditionally understood in relation to reductions in cerebral blood flow (CBF). However, a recent reanalysis of the flow-diffusion equation shows that increased capillary transit time heterogeneity (CTTH) can reduce the oxygen extraction efficacy in brain tissue for a given CBF. Changes in capillary morphology are typical of conditions predisposing to stroke and of experimental ischemia. Changes in capillary flow patterns have been observed by direct microscopy in animal models of ischemia and by indirect methods in humans stroke, but their metabolic significance remain unclear. We modeled the effects of progressive increases in CTTH on the way in which brain tissue can secure sufficient oxygen to meet its metabolic needs. Our analysis predicts that as CTTH increases, CBF responses to functional activation and to vasodilators must be suppressed to maintain sufficient tissue oxygenation. Reductions in CBF, increases in CTTH, and combinations thereof can seemingly trigger a critical lack of oxygen in brain tissue, and the restoration of capillary perfusion patterns therefore appears to be crucial for the restoration of the tissue oxygenation after ischemic episodes. In this review, we discuss the possible implications of these findings for the prevention, diagnosis, and treatment of acute stroke.Journal of Cerebral Blood Flow & Metabolism advance online publication, 27 February 2013; doi:10.1038/jcbfm.2013.18.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 02/2013; DOI:10.1038/jcbfm.2013.18 · 5.34 Impact Factor
  • Stroke 02/2013; 44(4). DOI:10.1161/STROKEAHA.111.000221 · 6.02 Impact Factor
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    ABSTRACT: OBJECTIVE: We qualitatively and quantitatively compared MRI enhancement obtained with gadofosveset, an albumin-binding blood-pool contrast agent, and with gadobutrol, an extracellular contrast agent, in patients with glioblastoma. METHODS: Thirty-five patients (25 men; 64 ± 14 years) with histologically proven glioblastoma underwent MRI including pre- and post-contrast T1-weighted SE images acquired 5 min after gadobutrol (0.1 mmol/kg) and, 48 h later, images acquired with identical parameters 5 min and 3, 6, and 24 h after gadofosveset (0.03 mmol/kg). Lesion extent, delineation, internal morphology, multifocality, and global diagnostic preference were evaluated quantitatively for the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and contrast enhancement (CE). RESULTS: Mean values of SNR, CNR, and tumour CE were highest 6 h after gadofosveset. Multifocality was seen in 17 (48.6 %) patients; additional lesions had stronger enhancement 6 h after gadofosveset in 12 patients (70.6 %). In 21 (60 %) patients, radiologists' global preference was highest in images acquired 6 h after gadofosveset (kappa = 0.764). In 22 patients (62.8 %), all qualitative endpoints were better at 5 min after gadobutrol than in images acquired 5 min after gadofosveset injection. CONCLUSIONS: Gadobutrol gives significant tumour enhancement in early postcontrast imaging. However, images acquired 6 h after gadofosveset injection have significantly better diagnostic information endpoints and contrast enhancement. KEY POINTS: • We compared MRI enhancement with gadofosveset and gadobutrol in patients with glioblastoma. • Gadobutrol provides better enhancement in early enhanced imaging at 5 min. • Gadofosveset at 6 h post-injection provides optimal enhancement and diagnostic information endpoints. • Gadofosveset is feasible for diagnostic quality contrast-enhanced MRI in glioblastoma. • The contrast medium dose can be reduced without disminishing the image quality using gadofosveset.
    European Radiology 10/2012; 23(4). DOI:10.1007/s00330-012-2678-9 · 4.34 Impact Factor
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    ABSTRACT: Fiber tracking is the most popular technique for creating white matter connectivity maps from diffusion tensor imaging (DTI). This approach requires a seeding process which is challenging because it is not clear how and where the seeds have to be placed. On the other hand, to enhance the interpretation of fiber maps, segmentation and clustering techniques are applied to organize fibers into anatomical structures. In this paper, we propose a new approach to automatically obtain bundles of fibers grouped into anatomical regions. This method applies an information-theoretic split-and-merge algorithm that considers fractional anisotropy and fiber orientation information to automatically segment white matter into volumes of interest (VOIs) of similar FA and eigenvector orientation. For each VOI, a number of planes and seeds is automatically placed in order to create the fiber bundles. The proposed approach avoids the need for the user to define seeding or selection regions. The whole process requires less than a minute and minimal user interaction. The agreement between the automated and manual approaches has been measured for 10 tracts in a DTI brain atlas and found to be almost perfect (kappa > 0.8) and substantial (kappa > 0.6). This method has also been evaluated on real DTI data considering 5 tracts. Agreement was substantial (kappa > 0.6) in most of the cases.
    Neuroinformatics 03/2012; 10(3):305-18. DOI:10.1007/s12021-012-9148-z · 3.10 Impact Factor
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    ABSTRACT: Little is known about the factors that determine recanalization after intravenous thrombolysis. We assessed the value of thrombus Hounsfield unit quantification as a predictive marker of stroke subtype and MCA recanalization after intravenous rtPA treatment. NCCT scans and CTA were performed on patients with MCA acute stroke within 4.5 hours of symptom onset. Demographics, stroke severity, vessel hyperattenuation, occlusion site, thrombus length, and time to thrombolysis were recorded. Stroke origin was categorized as LAA, cardioembolic, or indeterminate according to TOAST criteria. Two blinded neuroradiologists calculated the Hounsfield unit values for the thrombus and contralateral MCA segment. We used ROC curves to determine the rHU cutoff point to discriminate patients with successful recanalization from those without. We assessed the accuracy (sensitivity, specificity, and positive and negative predictive values) of rHU in the prediction of recanalization. Of 87 consecutive patients, 45 received intravenous rtPA and only 15 (33.3%) patients had acute recanalization. rHU values and stroke mechanism were the highest predictive factors of recanalization. The Matthews correlation coefficient was highest for rHU (0.901). The sensitivity, specificity, and positive and negative predictive values for lack of recanalization after intravenous rtPA for rHU ≤ 1.382 were 100%, 86.67%, 93.75%, and 100%, respectively. LAA thrombi had lower rHU than cardioembolic and indeterminate stroke thrombi (P = .004). The Hounsfield unit thrombus measurement ratio can predict recanalization with intravenous rtPA and may have clinical utility for endovascular treatment decision making.
    American Journal of Neuroradiology 12/2011; 33(1):90-6. DOI:10.3174/ajnr.A2878 · 3.68 Impact Factor
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    ABSTRACT: Multimodal visualization aims at fusing different data sets so that the resulting combination provides more information and understanding to the user. To achieve this aim, we propose a new information-theoretic approach that automatically selects the most informative voxels from two volume data sets. Our fusion criteria are based on the information channel created between the two input data sets that permits us to quantify the information associated with each intensity value. This specific information is obtained from three different ways of decomposing the mutual information of the channel. In addition, an assessment criterion based on the information content of the fused data set can be used to analyze and modify the initial selection of the voxels by weighting the contribution of each data set to the final result. The proposed approach has been integrated in a general framework that allows for the exploration of volumetric data models and the interactive change of some parameters of the fused data set. The proposed approach has been evaluated on different medical data sets with very promising results.
    11/2011; 18(9). DOI:10.1109/TVCG.2011.280

Publication Stats

320 Citations
140.04 Total Impact Points

Institutions

  • 2014
    • Instituto de Salud Carlos III
      • CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM)
      Madrid, Madrid, Spain
  • 2013–2014
    • IDIBGI Girona Biomedical Research Institute
      Girona, Catalonia, Spain
  • 2006–2014
    • Hospital Universitari de Girona Dr. Josep Trueta
      Girona, Catalonia, Spain
  • 2011
    • Universitat de Girona
      Girona, Catalonia, Spain
  • 2007
    • Clinica Girona
      Girona, Catalonia, Spain