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R Gilberto Gonzalez

Publications and source records attributed to R Gilberto Gonzalez.

At least 19 recordsLinked to original sources
PubMed2006

Serial diffusion tensor MRI after transient and permanent cerebral ischemia in nonhuman primates.

BACKGROUND AND PURPOSE: We measured the temporal evolution of the T2 and diffusion tensor imaging parameters after transient and permanent cerebral middle cerebral artery occlusion (MCAo) in macaques, and compared it to standard histological analysis at the study end point. METHODS: Stroke was created in adult male macaques by occluding a middle cerebral artery branch for 3 hours (transient MCAo, n=4 or permanent occlusion, n=3). Conventional MRI and diffusion tensor imaging scans were performed 0 (acute day), 1, 3, 7, 10, 17, and 30 days after MCAo. Animals were euthanized after the final scan and the brains removed for histological analysis. RESULTS: Apparent diffusion coefficient in the lesion was decreased acutely, fractional anisotropy was elevated, and T2 remained normal. Thereafter, apparent diffusion coefficient increased above normal, fractional anisotropy decreased to below normal, T2 increased to a maximum and then declined. Reperfusion at 3 hours accelerated these MRI changes. Only the fractional anisotropy value was significantly different between transient and permanent groups at 30 days. Final MRI-defined fractional lesion volumes were well correlated with corresponding histological lesion volumes. Permanent MCAO animals showed more severe histological damage than their transient MCAO counterparts, especially myelin damage and axonal swelling. CONCLUSIONS: Overall, the MRI evolution of stroke in macaques was closer to what has been observed in humans than in rodent models. This work supports the use of serial MRI in stroke studies in nonhuman primates.

Animals↗
PubMed2006

Astrocytic induction of matrix metalloproteinase-9 and edema in brain hemorrhage.

We tested the hypothesis that astrocytic matrix metalloproteinase-9 (MMP-9) mediates hemorrhagic brain edema. In a clinical case of hemorrhagic stroke, MMP-9 co-localized with astrocytes and neurons in peri-hematoma areas. In a mouse model where blood was injected into striatum, MMP-9 was colocalized with astrocytes surrounding the hemorrhagic lesion. Because MMP-9 is present in blood as well as brain, we compared four groups of wild type (WT) and MMP-9 knockout (KO) mice: WT blood injected into WT brain, KO blood into KO brain, WT blood into KO brain, and KO blood into WT brain. Gel zymography showed that MMP-9 was elevated in WT hemorrhagic brain tissue but absent from KO hemorrhagic brain tissue. Edematous water content was elevated when WT blood was injected into WT brain. However, edema was ameliorated when MMP-9 was absent in either blood or brain or both. To further assess the mechanisms involved in astrocytic induction of MMP-9, we next examined primary mouse astrocyte cultures. Exposure to hemoglobin rapidly upregulated MMP-9 in conditioned media within 1 to 24 h. Hemoglobin-induced MMP-9 was reduced by the free radical scavenger U83836E. Taken together, these data suggest that although there are large amounts of MMP-9 in blood, hemoglobin-induced oxidative stress can trigger MMP-9 in astrocytes and these parenchymal sources of matrix degradation may also be an important factor in the pathogenesis of hemorrhagic brain edema.

Animals↗
PubMed2006

Diffusion-weighted imaging in acute stroke.

Diffusion MR imaging has improved evaluation of acute ischemic stroke vastly. It is highly sensitive and specific in the detection of infarction at early time points when CT and conventional MR sequences are unreliable. The initial DWI lesion is believed to represent infarction core and usually progresses to infarction unless there is early reperfusion. The initial DWI lesion volume and ADC ratios correlate highly with final infarction volume and with acute and chronic neurologic assessment tests. ADC values may be useful in differentiating tissue destined to infarct from that potentially salvageable with reperfusion therapy. ADC values also may be useful for determining tissue at risk of HT after reperfusion therapy. DTI can quantify differences in the responses of gray versus white matter to ischemia. FA may be important in determining stroke onset time, and tractography provides early detection of wallerian degeneration that may be important in determining prognosis. Finally, DWI can determine which patients who have TIA are at risk for subsequent large vessel infarction and can differentiate stroke from stroke mimics. With improvements in MR software and hardware, diffusion MR undoubtedly will continue to improve the management of patients who have acute stroke.

Journal Article↗
PubMed2006

Functional magnetic resonance imaging measures of the effects of morphine on central nervous system circuitry in opioid-naive healthy volunteers.

In this pilot study, we used functional magnetic resonance imaging (fMRI) to study the effects of morphine in 8 healthy, opioid-naïve volunteers. Intravenous small-dose morphine (4 mg/70 kg) or saline was administered to volunteers undergoing a fMRI scan. Infusion of morphine, but not saline, elicited mild euphoria without aversive symptoms and resulted in positive signal changes in reward structures including the nucleus accumbens, sublenticular extended amygdala, orbitofrontal cortex, and hippocampus. The positive signal in the accumbens was opposite to the signal previously reported for noxious stimuli. Morphine produces a decreased signal in cortical areas in a similar manner to sedative-hypnotic drugs such as propofol or midazolam. Activation in endogenous analgesic regions was observed in the periaqueductal gray, the anterior cingulate gyrus (decreased signal), and hypothalamus (increased signals). The pattern of activation in reward circuitry was similar to that reported for euphoric drugs of abuse, providing a model to evaluate the initial effects of morphine on the central nervous system components of the circuitry involved in addiction. The segregation of fMRI response that was observed in cortical versus subcortical regions suggests a dissociation of reward from sensory-motor and cognitive functions. Activation patterns were opposite to those previously observed for the mu antagonist, naloxone.

Adult↗
PubMed2005

A pilot study of normobaric oxygen therapy in acute ischemic stroke.

BACKGROUND AND PURPOSE: Therapies that transiently prevent ischemic neuronal death can potentially extend therapeutic time windows for stroke thrombolysis. We conducted a pilot study to investigate the effects of high-flow oxygen in acute ischemic stroke. METHODS: We randomized patients with acute stroke (<12 hours) and perfusion-diffusion "mismatch" on magnetic resonance imaging (MRI) to high-flow oxygen therapy via facemask for 8 hours (n=9) or room air (controls, n=7). Stroke scale scores and MRI scans were obtained at baseline, 4 hours, 24 hours, 1 week, and 3 months. Clinical deficits and MR abnormalities were compared between groups. RESULTS: Stroke scale scores were similar at baseline, tended to improve at 4 hours (during therapy) and 1 week, and significantly improved at 24 hours in hyperoxia-treated patients. There was no significant difference at 3 months. Mean (+/-SD) relative diffusion MRI lesion volumes were significantly reduced in hyperoxia-treated patients at 4 hours (87.8+/-22% versus 149.1+/-41%; P=0.004) but not subsequent time points. The percentage of MRI voxels improving from baseline "ischemic" to 4-hour "non-ischemic" values tended to be higher in hyperoxia-treated patients. Cerebral blood volume and blood flow within ischemic regions improved with hyperoxia. These "during-therapy" benefits occurred without arterial recanalization. By 24 hours, MRI showed reperfusion and asymptomatic petechial hemorrhages in 50% of hyperoxia-treated patients versus 17% of controls (P=0.6). CONCLUSIONS: High-flow oxygen therapy is associated with a transient improvement of clinical deficits and MRI abnormalities in select patients with acute ischemic stroke. Further studies are warranted to investigate the safety and efficacy of hyperoxia as a stroke therapy.

Adult↗
PubMed2005

Dynamic susceptibility contrast perfusion imaging of cerebral ischemia in nonhuman primates: comparison of Gd-DTPA and NMS60.

PURPOSE: To study a new gadolinium (Gd) contrast agent-NMS60-for MR perfusion-weighted imaging (PWI) of brain tissue. MATERIALS AND METHODS: NMS60 is a Gd3+ trimer with a molecular weight of 2158 Daltons, and a T2 relaxivity almost three times higher than that of Gd-DTPA. Middle cerebral artery (MCA) occlusion was induced in nine nonhuman primates. The animals were scanned acutely and for up to six follow-up time points. PWI peak, and time-to-peak maps were generated, and perfusion deficit volumes were measured from these maps. The values of peak, time-to-peak, and perfusion deficit volume were compared between NMS60 and GD-DTPA. RESULTS: These results demonstrate that there was no significant difference in our calculated perfusion parameters between the two contrast agents. CONCLUSION: The two agents were found to be equally effective for PWI for acute and chronic stroke in primates. Along with its previously demonstrated advantage for T1-enhanced imaging, the current results show that NMS60 is a viable contrast agent for use in stroke patients.

Animals↗
PubMed2005

Quantification of phosphocholine and glycerophosphocholine with 31P edited 1H NMR spectroscopy.

Choline and the related compounds phosphocholine (PC) and glycerophosphocholine (GPC) are considered to be important metabolites in oncology. Past studies have demonstrated correlations linking the relative ratios and concentrations of these metabolites with the development and progression of cancer. Currently, in vivo and tissue ex vivo magnetic resonance spectroscopy methods have mostly centered on measuring the total concentration of these metabolites and have difficulty in differentiating between them. Here, a new scheme that uses (31)P edited (1)H spectroscopy to quantify the concentrations of choline, PC and GPC in biological samples is reported and its applicability is demonstrated using samples of human brain tumor extracts. This method is particularly well-suited for analytical situations where the PC and GPC resonances are not sufficiently resolved and/or are obscured by other metabolites. Consequently, this scheme has the potential to be used for the analysis of choline compounds in ex vivo tissue samples.

Biomarkers, Tumor↗
PubMed2005

Diffusion-weighted imaging in acute stroke.

In magnetic resonance diffusion-weighted imaging (DWI), regions of the brain are depicted not only on the basis of physical properties, such as T2 relaxation and spin density, which influence image contrast in conventional MR imaging, but also by local characteristics of water molecule diffusion. The diffusion of water molecules is altered in a variety of disease processes, including ischemic stroke. The changes that occur in acute infarction enable DWI to detect very early ischemia. Also, because predictable progression of diffusion findings occurs during the evolution of ischemia, DWI enables more precise estimation of the time of stroke onset than does conventional imaging.

Brain↗
PubMed2005

MRI in treatment of adult gliomas.

Diffuse astrocytomas of the adult cerebral hemispheres are unique among tumours in human beings in the extent to which their imaging features are related to histopathological characteristics and clinical behaviour. However, understanding is still restricted about the value of imaging features in the measurement of response and of progression in these tumours. The present approach used in clinical trials, which consists of an anatomical measurement of the enhancing tumour on MRI, has many problems, and might not be acceptable as a surrogate endpoint for survival in patients with glioblastoma who are enrolled in clinical trials. Dynamic imaging techniques, such as capillary permeability mapping, are being used in studies of new drugs that target specific molecular features of gliomas; however, the validity of these techniques has not been elucidated. Diffusion imaging can be valuable for fibre-tract mapping to assist surgical planning and might become useful in measuring early response to treatment in densely cellular tumours. Functional imaging techniques can be used to localise motor, sensory, and language-control areas before surgery. Intraoperative MRI has produced improvements in the extent of tumour resection, and molecular imaging is another technique on the horizon, which could come to have a role in clinical trials in the near future. Thus, as a rapidly expanding sphere of investigation, brain-tumour imaging is producing great excitement. The aim of these new techniques is to aid the identification of more effective treatments.

Adult↗
PubMed2005

Radiation necrosis versus glioma recurrence: conventional MR imaging clues to diagnosis.

BACKGROUND AND PURPOSE: Conventional MR imaging findings are considered to be inadequate for reliably distinguishing radiation necrosis from tumor recurrence in patients with glioma. Despite this belief, we hypothesized that certain conventional MR imaging findings, alone or in combination, though not definitive, may favor one or another of these diagnoses in proton beam-treated patients with new enhancing lesions on serial scanning. METHODS: MR imaging findings (axial T1-, T2-, and post-gadolinium T1-weighted) of 27 proton beam radiation therapy patients with high-grade gliomas were retrospectively reviewed. Entry criteria included new MR imaging enhancing lesions after treatment and histologically unequivocal biopsy proof of diagnosis. Readers rated corpus callosum involvement, midline spread, subependymal spread, new discrete multiple enhancing foci, a "spreading wavefront" appearance, and septum pellucidum involvement. Statistical analysis was by the Fisher exact test. RESULTS: Corpus callosum involvement in combination with multiple other findings was highly associated with progressive glioma. These combinations included involvement of the corpus callosum with multiple enhancing foci (P = .02), involvement of the corpus callosum with crossing the midline and multiple enhancing lesions (P = .04), and involvement of the corpus callosum with subependymal spread and multiple enhancing lesions (P = .01). CONCLUSIONS: In proton beam-treated patients with glioma, corpus callosum involvement, in conjunction with multiple enhancing lesions with or without crossing of the midline and subependymal spread, favors predominant glioma progression. Overall, combinations of enhancement patterns were more likely than individual patterns to distinguish necrosis from predominant tumor progression. Together with clinical and functional imaging findings, these results may assist in determining the need for biopsy.

Aged↗
PubMed2005

Intracranial hemorrhage complicating acute stroke: how common is hemorrhagic stroke on initial head CT scan and how often is initial clinical diagnosis of acute stroke eventually confirmed?

BACKGROUND AND PURPOSE: Assessment of possible hemorrhage in acute stroke before appropriate therapy remains important. The aim of this study was to determine the frequency with which patients present with clinical stroke and have intracranial hemorrhage on initial noncontrast head CT scan (NCCT). In addition, we sought to determine the frequency with which initial clinical diagnosis acute stroke is confirmed in this group. METHODS: Medical records of 691 consecutive patients with admitting diagnosis of acute stroke were evaluated retrospectively. Results of initial NCCT performed within 24 hours after presentation were assessed. All patients were examined before anticoagulation or thrombolysis. Correlation with treatment and leading differential etiology was made. RESULTS: Twenty-five patients (25/691 [3.6%]) had hemorrhage. Twenty-three patients (23/25 [92%]) had intraparenchymal hemorrhage only. One patient (1/25 [4%]) had a combination of intraparenchymal and subarachnoid hemorrhage. One patient (1/25 [4%]) had subdural hemorrhage only. Twenty-two NCCT scans (22/25 [88%]) were performed within 6 hours of presentation. Seventeen NCCT scans (17/25 [68%]) were performed within 3 hours of presentation. CONCLUSION: Despite frequent concerns for intracranial hemorrhage complicating acute stroke and treatment, a low percentage of patients had this complication. Moreover, our frequency is much lower than the wide ranges reported elsewhere. The most common type of intracranial hemorrhage in this cohort was intraparenchymal, but subarachnoid and subdural hemorrhages were also diagnosed and must also be considered. Twenty-eight percent of patients with initial suspicion of acute ischemic stroke are eventually given other diagnoses. These results may have implications for use of CT imaging.

Adult↗
PubMed2004

MRI changes in the rat hippocampus following proton radiosurgery.

PURPOSE: To define radiographic dose-response relationships for proton radiosurgery using a rat brain model. METHODS AND MATERIALS: A group of 23 rats was treated with Bragg peak proton beam irradiation involving the right hippocampus. Single doses of 5, 12, 20, 30, 60, 90 and 130 cobalt gray equivalents (CGE) were delivered to groups of 3 animals using single fraction technique. One extra animal was included at the 130- and 30-CGE doses. Animals were imaged using a standard 1.5-tesla GE Signa MRI. A 3-inch surface coil was employed to obtain T1-weighted sagittal images (TR 600 and TE 30) and dual echo T2-weighted coronal images (TR 3,000 and TE 30/90). Animals were imaged at 1.5, 3, 4.5, 6 and 9 months. Volumetric analysis with custom software was done to evaluate areas of increased signal on T2-weighted images, and signal change versus time curves were generated. Gadolinium-enhanced T1-weighted imaging was also done at the 9-month time point to further evaluate tissue injury. The development of hydrocephalus was also examined. RESULTS: Peak tissue injury was greater and occurred earlier with higher versus lower doses of radiation. Statistically significant differences were seen between the 130- and 90-CGE animals and between the 90- and 60-CGE animals (p < 0.0016) using ANOVA. Signal changes can be seen in at least 1 of the animals at 20 CGE. The largest volume of tissue enhancement at 9 months was seen in animals at 60 CGE, which may represent an intermediate zone of tissue injury and gliosis compared with greater tissue loss at higher doses and less injury at lower doses. Hydrocephalus developed first in the untreated hemisphere in 130- and 90-CGE animals as a result of mass effect while it occurred at a later time in the treated hemisphere in lower-dose animals. CONCLUSIONS: Following single-dose proton radiosurgery of rat hippocampus, serial MRIs show T2 signal changes in animals ranging from 130 down to 20 CGE as well as the development of hydrocephalus. Dose-effect relationships using proton radiosurgery in rats will be a helpful step in guiding further studies on radiation injury to brain tissue.

Animals↗
PubMed2004

ASPECTS on CTA source images versus unenhanced CT: added value in predicting final infarct extent and clinical outcome.

BACKGROUND AND PURPOSE: The Alberta Stroke Program Early CT Score (ASPECTS) is a grading system to assess ischemic changes on CT in acute ischemic stroke. CT angiography-source images (CTA-SI) predict final infarct volume. We examined whether the final infarct ASPECTS and clinical outcome were more related to acute CTA-SI ASPECTS than to the acute noncontrast CT (NCCT) ASPECTS. METHODS: ASPECTS was assigned by 2 raters on the acute NCCT, CTA-SI, and follow-up imaging. The mean baseline ASPECTS of acute NCCT and CTA-SI was compared with the follow-up ASPECTS. Rate ratios (RRs) were used to quantify the relationship between the dichotomized baseline ASPECTS (categorized as 0 to 7 versus 8 to 10) and favorable patient outcome. RESULTS: Thirty-nine patients were recruited. Proximal occlusion (internal carotid artery or middle cerebral artery) was seen in 62%, M2 occlusion in 18%, and no occlusion was seen in 20% of patients. The median time between symptom onset and imaging was 1.9 (1.2 to 2.5) hours. There was a significantly larger difference of 1.4 between the mean baseline NCCT and CTA-SI ASPECTS in patients who had more ischemic changes (follow-up ASPECTS=0 to 3) than a difference of 0.6 in patients who had near-to-normal CT scans (follow-up ASPECTS=8 to 10). The rate of favorable outcome for acute NCCT ASPECTS of 8 to 10 was 51.8% versus 25.0% for 0 to 7 (RR, 2.1, 95% CI: 0.7 to 5.9, P=0.12). For acute CTA-SI ASPECTS of 8 to 10, the rate of favorable outcome was 58.8% versus 31.8% for 0 to 7 (RR, 1.8, 95% CI: 0.9 to 3.8, P=0.09). CONCLUSIONS: CTA-SI ASPECTS provides added information in the prediction of final infarct size.

Aged↗