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Biomedical subjects

R G Gonzalez

Publications and source records attributed to R G Gonzalez.

At least 19 recordsLinked to original sources

Clinical and radiographic features of peritumoral infarction following resection of glioblastoma.

Focal areas of restricted diffusion adjacent to high-grade glioma resection cavities were detected in 70% of patients on immediate postoperative MRI studies. Follow-up studies demonstrated cystic encephalomalacia in 91% of these foci, suggesting the presence of infarction, and the infarcted tissue demonstrated enhancement in 43% of cases. New postoperative deficits correlated well with the anatomic region of infarction in six patients. Enhancement in perioperative infarcts can mimic tumor progression on follow-up imaging studies.

Adult↗

MR spectroscopic changes in the rat hippocampus following proton radiosurgery.

PURPOSE: To identify MR spectroscopic changes in the rat hippocampus following proton radiosurgery. METHODS AND MATERIALS: A group of 12 rats were treated with Bragg peak proton beam irradiation involving the right hippocampus. Single doses of 30 CGE, 50 CGE, 70 CGE, 90 CGE were delivered to groups of 3 animals using single fraction technique. Animals were imaged using a standard 3 T GE Signa MRI at 4 months following treatment. An untreated animal was also studied. A 3'' surface coil was employed to obtain T1 weighted coronal pre- and post-gadolinium images (TR 600 and TE 30) and dual echo T2 weighted coronal images (TR 3000, TE 30/90). Volumetric analysis with custom software was done to evaluate areas of increased signal on T2 weighted images and the development of hydrocephalus was examined. Animals were sacrificed and specimens of the treated hippocampus were harvested for High Resolution Magic Angle Spinning MR Spectroscopy (HRMAS) followed by histopathology of the tissue samples. Peak values of choline, creatine, N-acetyl aspartate and lipids were evaluated and compared. RESULTS: Peak tissue injury occurred in the surviving 90 CGE animal by both T2 weighted and post-gadolinium imaging. Gadolinium enhancement was seen in decreasing volumes of tissue at dosage levels from 90 to 50 CGE. Hydrocephalus was seen on the untreated side in the 90 CGE animal likely because of mass effect, while it was seen in small degrees in the side of treatment in the 70 and 50 CGE animals. Histopathology showed changes at 90 and 70 CGE, but not at 50 or 30 CGE at this time point using H and E stains. HRMAS showed spectroscopic changes in the surviving 90 and 70 CGE animals but not in the 50 and 30 CGE animals. Statistical significance was not reached because of the small sample size. CONCLUSIONS: Following single dose proton radiosurgery of rat hippocampus, HRMAS is able to identify metabolic changes induced by radiation. Studies built on these principles may help develop non-invasive MR spectroscopic methods to distinguish radiation changes from tumor recurrence.

Animals↗

First-pass quantitative CT perfusion identifies thresholds for salvageable penumbra in acute stroke patients treated with intra-arterial therapy.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether, in acute stroke patients treated with intra-arterial (IA) recanalization therapy, CT perfusion (CTP) can distinguish ischemic brain tissue destined to infarct from that which will survive. METHODS: Dynamic CTP was obtained in 14 patients within 8 hours of stroke onset, before IA therapy. Initial quantitative cerebral blood volume (CBV) and flow (CBF) values were visually segmented and normalized in the "infarct core" (region 1: reduced CBV and CBF, infarction on follow-up), "penumbra that infarcts" (region 2: normal CBV, reduced CBF, infarction on follow-up), and "penumbra that recovers" (region 3: normal CBV, reduced CBF, normal on follow-up). Normalization was accomplished by dividing the ischemic region of interest value by that of a corresponding, contralateral, uninvolved region, which resulted in CBV and CBF "ratios." Separate CBV and CBF values were obtained in gray matter (GM) and white matter (WM). RESULTS: Mean CBF ratios for regions 1, 2, and 3 were 0.19 +/- 0.06, 0.34 +/- 0.06, and 0.46 +/- 0.09, respectively (all P < .001). Mean CBV ratios for regions 1, 2, and 3 were similarly distinct (all P < .05). Absolute CBV and CBF values for regions 2 and 3 were not significantly different. All regions with CBF ratio <0.32, CBV ratio <0.68, CBF <12.7 mL/100 g/min, or CBV <2.2 mL/100 g infarcted. No region with CBF ratio >0.44 infarcted. GM versus WM CBF and CBV values were significantly different for region 2 compared with region 3 (P < .05). CONCLUSIONS: In acute stroke patients, quantitative CTP can distinguish ischemic tissue likely to infarct from that likely to survive.

Adult↗

Diagnostic evaluation of patients with a brain mass as the presenting manifestation of cancer.

BACKGROUND: Patients with a newly detected brain mass and no history of cancer often undergo extensive diagnostic testing in search of a systemic primary neoplasm prior to selection of a biopsy site, potentially leading to unnecessary expense and delay. We sought patterns in the evaluation of these patients to allow rapid selection of a biopsy site. METHODS: We compared the diagnostic evaluation of 176 patients with newly detected brain masses who were ultimately determined to have a metastatic or primary lesion. RESULTS: In 88 patients presenting with brain metastasis, lung cancer was markedly overrepresented as a primary tumor, occurring in 82% of patients. Brain MRI and chest CT together identified the site for diagnostic biopsy in all except for two of the 176 patients. One-half of the patients with metastasis had brain biopsy as the primary diagnostic procedure, with 80% undergoing a craniotomy rather than needle biopsy. The initial management decision in the majority of metastasis patients was whether to perform a craniotomy for resection of tumor. Whereas patients with single and cerebellar lesions were most likely to undergo craniotomy, the extent of systemic disease did not affect the decision to recommend a neurosurgical procedure. The average time to biopsy for patients with metastatic and primary tumors was 4.7 days and 6.0 days. In this retrospective population, we estimated that evaluation with brain MRI and chest CT, followed by an early neurosurgical decision, could reduce the time to diagnosis by at least 10%. CONCLUSIONS: Chest CT and brain MRI, if used together as initial diagnostic studies, would have identified a biopsy site in 97% of patients with a newly detected brain mass.

Biopsy↗

HIV leucoencephalopathy and TNFalpha expression in neurones.

BACKGROUND: Human immunodeficiency virus (HIV) leucoencephalopathy (HIVL) is an uncommon and rapidly progressive form of AIDS dementia complex (ADC) that has remained poorly understood. Tumour necrosis factor alpha (TNFalpha), which has been implicated in the pathogenesis of ADC, is predominantly localised in macrophages in the HIV infected brain, although in vitro studies indicate that neurones can express this cytokine. OBJECTIVE: To examine the clinical/neuroradiological features of HIVL and the expression of TNFalpha in HIVL. METHODS: Six patients who presented with rapidly progressive dementia within four to 12 weeks of the primary manifestation of their HIV infection were evaluated. Clinical history, treatment regimens, and imaging studies were reviewed, and brain samples from three of the patients were studied by means of immunohistochemistry. RESULTS: Imaging studies showed diffuse bilateral deep white matter changes in all six patients. Clinical and imaging abnormalities improved in five of the six patients within weeks after initiation of antiretroviral treatment. Brain biopsies of two showed pronounced microglia/macrophage activation, but only scant viral protein (gp41) expression. Staining for TNFalpha was found in microglia/macrophages, and surprisingly, in neurones also. Postmortem analysis of a third patient also showed TNFalpha expression in neurones of the frontal cortex and basal ganglia. CONCLUSION: This study provides the first demonstration of staining for TNFalpha in the neurones of the HIV infected brain, and suggests that the process underlying this rapidly progressive form of ADC may reflect indirect mechanisms mediated by host factors, particularly TNFalpha.

AIDS Dementia Complex↗

fMRI measurement of CNS responses to naloxone infusion and subsequent mild noxious thermal stimuli in healthy volunteers.

The aims of this study were to assess the effects of a mu-opioid antagonist, naloxone, on endogenous opioid systems and to evaluate the effect of naloxone on the CNS response to mild noxious heat. Doubled-blinded experiments were performed in a cross-over design in 10 healthy male volunteers. Functional magnetic resonance imaging (fMRI) data were collected before and during the infusion and also during thermal stimuli. Increased signal was observed in a number of cortical and subcortical brain regions for naloxone versus saline infusion. Cortical activation was induced in regions including cingulate, prefrontal cortex, and insula. Subcortical regions showing increased signal change included hippocampus and entorhinal cortex. A 46 degrees C stimulus delivered to the back of the hand induced an overall increase in activation in a number of regions in the naloxone group that were not seen in the saline group (e.g., insula, orbitofrontal cortex, thalamus, and hippocampus). These results show that naloxone, even in the absence of psychophysical effects, produces activation in several brain regions that are known to have high levels of mu-opioid receptors and may be involved in endogenous analgesia. Our study is an example of how fMRI can measure subtle changes in brain activation induced by pharmacological agents without cognitive effects.

Adult↗

Diffusion-weighted MRI in diffuse axonal injury of the brain.

The goal of this study was to identify and describe the different types and patterns of tissue injury which are encountered by diffusion-weighted imaging (DWI) in diffuse axonal injury (DAI) of the brain. The DWI data sets of 98 patients who suffered from a closed-head injury were retrospectively evaluated. Medical records were reviewed to rule out pre-existing neurological diseases. Lesions were studied for their DWI signal characteristics and lesion size or extension. Traumatic lesions were classified into three categories depending on their signal characteristica on DWI and apparent diffusion coefficient (ADC) maps: type 1, DWI- and ADC-hyperintense most likely representing lesions with vasogenic edema; type 2, DWI-hyperintense, ADC-hypointense indicating cytotoxic edema; type 3, central hemorrhagic lesion surrounded by an area of increased diffusion. According to the size and extent of lesions, injury was classified into three groups: group A, focal injury; group B, regional/confluent injury; and group C, extensive/diffuse injury. Our study showed that diffusion-weighted imaging differentiates between lesions with decreased and increased diffusion in patients with DAI. Different degrees of tissue injury extent were noticed. Future prospective studies should study if this additional information can be used as a predictor of injury reversibility, final outcome and prognosis.

Adolescent↗

Magnetic resonance spectroscopy: an in vivo tool for monitoring cerebral injury in SIV-infected macaques.

The purpose of our study was to demonstrate the feasibility of using in vivo proton Magnetic Resonance Spectroscopy (MRS) to monitor the brain manifestations of SIV infection in the macaque model of AIDS. Previous spectroscopy work on macaque brain tissue and in vivo work in humans is reviewed to provide the motivation and context for this study. We collected 34 MRS data sets on 14 uninfected rhesus macaques. From this data, we demonstrate that we are capable of detecting changes similar to those observed in human MRS studies for most metabolites using less than 10 animals. The juvenile macaques utilized in this study demonstrate age-related changes in the levels of N-acetyl aspartate (NAA), a neuronal marker. The quantity and distribution of neurochemicals in the macaque are found to be slightly, but significantly, different than in the human.

Aging↗

Reward circuitry activation by noxious thermal stimuli.

Using functional magnetic resonance imaging (fMRI), we observed that noxious thermal stimuli (46 degrees C) produce significant signal change in putative reward circuitry as well as in classic pain circuitry. Increases in signal were observed in the sublenticular extended amygdala of the basal forebrain (SLEA) and the ventral tegmentum/periaqueductal gray (VT/PAG), while foci of increased signal and decreased signal were observed in the ventral striatum and nucleus accumbens (NAc). Early and late phases were observed for signals in most brain regions, with early activation in reward related regions such as the SLEA, VT/PAG, and ventral striatum. In contrast, structures associated with somatosensory perception, including SI somatosensory cortex, thalamus, and insula, showed delayed activation. These data support the notion that there may be a shared neural system for evaluation of aversive and rewarding stimuli.

Adult↗

Diffusion MRI in ischemic stroke compared to pathologically verified infarction.

BACKGROUND: Diffusion MRI abnormality correlates with pathology in animal ischemic stroke models. A combined retrospective and prospective analysis of consecutive patients over a 3-year period who had a clinical diagnosis of probable new ischemic stroke, underwent diffusion MRI, and were later studied at autopsy was performed. METHODS: Inclusion criteria for the retrospective analysis were 1) symptom onset within 14 days of presentation, 2) diffusion MRI within 28 days of symptom onset, and 3) autopsy within 16 weeks of symptom onset. Patients with suspected further infarcts between MRI and autopsy were excluded. The locations of all areas of MRI abnormality were identified by a blinded neuroradiologist, and recent infarcts were identified by review of pathologic records and microscopic slides. RESULTS: Eleven patients were identified who fulfilled inclusion criteria, with 25 discrete pathologic infarcts. Diffusion MRI abnormality corresponded to pathologically verified infarction in 23 cases, was present in two locations where no pathologic infarct was identified, and was absent in two locations where an infarct was present at autopsy. In two cases, despite clinical suspicion of acute ischemic stroke, no MRI abnormality or pathologic infarct was found. The sensitivity and specificity of diffusion MRI were 88.5% (95% CI, 69.9% to 97.6%) and 96.6% (95% CI, 91.5% to 99.1%). Accuracy was 95.1% (95% CI, 90.2% to 98%). Three further patients who died during the course of the retrospective analysis were studied prospectively, and are described separately. CONCLUSIONS: These findings suggest high accuracy of diffusion MRI for detection of ischemic infarction compared with pathologic examination.

Adult↗

Non-destructive quantitation of spermine in human prostate tissue samples using HRMAS 1H NMR spectroscopy at 9.4 T.

We present the results of a study of human prostate specimens evaluated by high resolution magic angle spinning (1)H nuclear magnetic resonance (NMR) spectroscopy at 400 MHz (9.4 T) and by quantitative histopathology. We demonstrate that NMR and pathology data can be obtained from the same intact specimens, and report for the first time a linear correlation between the NMR measured concentration of spermine, a proposed endogenous inhibitor to prostate cancer growth, and the volume percentage of normal prostatic epithelial cells as quantified by histopathology. Our results show that NMR may serve as a critical tool for the investigation of the inhibitory mechanism of spermine in human subjects.

Humans↗

Diagnostic value of apparent diffusion coefficient hyperintensity in selected patients with acute neurologic deficits.

BACKGROUND AND PURPOSE: A pattern of decreased intensity on apparent diffusion coefficient (ADC) maps is useful in the early detection of ischemic brain injury. Less information exists with regard to patients with acute neurologic deficits in whom there is abnormal conventional magnetic resonance imaging (MRI) and increased ADC intensity. METHODS: The authors identified 13 patients with acute neurologic deficits who underwent diffusion MRI and had calculated ADC maps demonstrating hyper-intensity in regions characterized by computed tomography hypodensity and MRI T2 hyperintensity. The initial and follow-up imaging characteristics and clinical syndromes were recorded. RESULTS: Clinical syndromes included hypertensive encephalopathy, posterior leukoencephalopathy, hyperperfusion following carotid endarterectomy, venous sinus thrombosis, HIV encephalopathy, and brain tumor. Diffusion-weighted imaging (DWI) was hyperintense in 3 of 13 patients, isointense in 4 of 13 patients, heterogeneous in 3 of 13 patients, and hypointense in 3 of 13 patients. The ADC values in these regions were significantly higher than those in control regions (P < .0001). At early follow-up, MRI abnormalities resolved completely in 3 of 13 patients and partially in 9 of 13 patients. MRI abnormalities were unchanged in 1 patient. CONCLUSIONS: In the evaluation of patients with acute neurologic deficits, ADC hyperintensity may identify a subset of patients with vasogenic edema of nonischemic etiology. Frequently, these conditions are potentially reversible if appropriately managed. DWI and conventional images alone are not sufficient to identify these neurologic conditions.

Acute Disease↗

Frequency and clinical context of decreased apparent diffusion coefficient reversal in the human brain.

PURPOSE: To determine the probability that regions of decreased apparent diffusion coefficient (ADC) return to normal without persistent symptoms or T2 change and the settings in which these ADC reversals occur. MATERIALS AND METHODS: Three hundred magnetic resonance (MR) imaging studies were selected at random from a database of 7,147 examinations to determine the probability of a pathologically decreased ADC. In cases with decreased ADC, the clinical history was recorded and, if available, follow-up MR imaging findings were evaluated. Five cases of ADC reversal became known during the same period and were evaluated to determine the initial ADC decrease, clinical outcome, and findings at follow-up imaging. RESULTS: Findings in 116 of 300 MR imaging studies revealed regions of decreased ADC. In 49 of 116 studies, follow-up MR imaging examinations were performed at least 4 weeks after the onset of symptoms; ADC did not reverse. Five cases of ADC reversal were identified in the same period, giving an estimated 0.2%-0.4% probability of ADC reversal. Clinical settings were venous sinus thrombosis and seizure (n = 3), hemiplegic migraine (n = 1), and hyperacute arterial infarction (n = 1). Both white matter (n = 3) and gray matter (n = 3) regions were involved. CONCLUSION: Reversal of ADC lesions is rare, occurs in complicated clinical settings, and can involve white or gray matter.

Adolescent↗

Predicting tissue outcome in acute human cerebral ischemia using combined diffusion- and perfusion-weighted MR imaging.

BACKGROUND AND PURPOSE: Tissue signatures from acute MR imaging of the brain may be able to categorize physiological status and thereby assist clinical decision making. We designed and analyzed statistical algorithms to evaluate the risk of infarction for each voxel of tissue using acute human functional MRI. METHODS: Diffusion-weighted MR images (DWI) and perfusion-weighted MR images (PWI) from acute stroke patients scanned within 12 hours of symptom onset were retrospectively studied and used to develop thresholding and generalized linear model (GLM) algorithms predicting tissue outcome as determined by follow-up MRI. The performances of the algorithms were evaluated for each patient by using receiver operating characteristic curves. RESULTS: At their optimal operating points, thresholding algorithms combining DWI and PWI provided 66% sensitivity and 83% specificity, and GLM algorithms combining DWI and PWI predicted with 66% sensitivity and 84% specificity voxels that proceeded to infarct. Thresholding algorithms that combined DWI and PWI provided significant improvement to algorithms that utilized DWI alone (P=0.02) but no significant improvement over algorithms utilizing PWI alone (P=0.21). GLM algorithms that combined DWI and PWI showed significant improvement over algorithms that used only DWI (P=0.02) or PWI (P=0.04). The performances of thresholding and GLM algorithms were comparable (P>0.2). CONCLUSIONS: Algorithms that combine acute DWI and PWI can assess the risk of infarction with higher specificity and sensitivity than algorithms that use DWI or PWI individually. Methods for quantitatively assessing the risk of infarction on a voxel-by-voxel basis show promise as techniques for investigating the natural spatial evolution of ischemic damage in humans.

Acute Disease↗

Utility of perfusion-weighted CT imaging in acute middle cerebral artery stroke treated with intra-arterial thrombolysis: prediction of final infarct volume and clinical outcome.

BACKGROUND AND PURPOSE: The goal of this study was to evaluate the utility of perfusion-weighted CT (PWCT) in predicting final infarct volume and clinical outcome in patients with acute middle cerebral artery (MCA) stroke. METHODS: Twenty-two consecutive patients with MCA stem occlusion who underwent intra-arterial thrombolysis within 6 hours of stroke onset had noncontrast CT and CT angiography with whole-brain PWCT imaging before treatment. Infarct volumes were computed from the initial PWCT and follow-up scans; clinical outcome was measured with the modified Rankin scale. RESULTS: Initial PWCT lesion volumes correlated significantly with final infarct volume (P=0.0002) and clinical outcome (P=0.01). For the 10 patients with complete recanalization, the relationship between initial and final lesion volume was especially strong (R(2)=0.94, P<0.0001, slope of regression line=0.92). For those without complete recanalization, there was progression of lesion volume on follow-up imaging (R(2)=0.50, P=0.01, slope of regression line=1.61). All patients with either initial PWCT lesion volumes >100 mL or no recanalization had poor outcomes (Rankin scores, 4 to 6). Mean admission NIH Stroke Scale scores and mean lesion volumes in the poor outcome group were significantly different compared with the good or fair outcome (Rankin scores, 0 to 3) group (21+/-4 versus 17+/-5, P=0.05, and 106+/-79 versus 29+/-37 mL, P=0.01). Patients with initial volumes <100 mL and partial or complete recanalization all had good (Rankin scores, 0 to 2) or fair (Rankin score, 3) outcomes. CONCLUSIONS: Lesion volumes on admission PWCT images approximate final infarct volume for patients with early complete recanalization of MCA stem occlusion. For those without complete recanalization, there is subsequent enlargement of lesion volume on follow-up. Initial PWCT lesion volumes also have predictive value; volumes >100 mL are associated with a poor clinical outcome. In these highly selected patients, initial PWCT lesion volume was a stronger predictor of clinical outcome than was initial NIH Stroke Scale score.

Acute Disease↗

Unique linear and nodular MR enhancement pattern in schistosomiasis of the central nervous system: report of three patients.

OBJECTIVE: The purpose of this paper is to describe the unique MR imaging appearance of schistosomiasis of the central nervous system (CNS). CONCLUSION: Contrast-enhanced T1-weighted MR images in all three patients with CNS schistosomiasis revealed a central linear enhancement surrounded by multiple enhancing punctate nodules, forming an "arborized" appearance. Pathologically, this enhancement pattern correlated with a host granulomatous response to Schistosoma species ova. Although the pattern is not present in all cases of CNS schistosomiasis, when it is observed, a diagnosis of CNS schistosomiasis should be considered.

Adult↗

Silent thromboembolic events associated with the treatment of unruptured cerebral aneurysms by use of Guglielmi detachable coils: prospective study applying diffusion-weighted imaging.

BACKGROUND AND PURPOSE: Aneurysm embolization using Guglielmi detachable coils (GDC) is gaining increasing acceptance as a viable alternative to surgery in the treatment of cerebral aneurysms. Although recent reports describe a significant rate of symptomatic thromboembolic complications with GDC use, many of the neurologic deficits are transient. We sought to determine the incidence of silent thromboembolic events with the use of diffusion-weighted imaging and to correlate radiologic findings with the results of neurologic examinations. METHODS: Diffusion-weighted MR imaging was performed within 48 hours in 14 consecutive elective GDC aneurysm treatments. Embolizations were performed under systemic heparinization; all flush solutions were heparinized, and both guiding catheters and microcatheters were placed for continuous heparinized infusions. Neurologic examination, including the National Institutes of Health Stroke Scale determination, was performed by a stroke neurologist before the coiling procedures were performed, immediately after the procedures were performed, and before discharge. MR imaging examinations were reviewed by a stroke neurologist and an interventional neuroradiologist, with determination and characterization of diffusion-weighted imaging abnormalities. RESULTS: Small areas of restricted diffusion, presumed to represent procedure-related embolic infarctions, were noted on the images of eight of 14 patients. All except one of the areas were located ipsilateral to the side of the catheterization. Six patients had evidence of multiple infarcts. Most lesions were small (<2 mm); one patient with coil stretch and herniation into the parent vessel had numerous infarcts with a dominant posterior frontal infarct. Pre- and posttreatment National Institutes of Health Stroke Scale scores were unchanged for 13 of 14 patients. Overall, the rate of asymptomatic emboli was 61% (eight of 13 treatments) in uncomplicated treatments. Strokes occurred independently of the number of coils used; the mean number of coils used for patients with strokes was 7.6 (range, two to 13) and for patients without evidence of infarcts was 10.2 (range, one to 30). This was not a significant difference (P > .5). CONCLUSION: Silent thromboembolic events related to the use of the GDC system are a common occurrence, despite meticulous technique and systemic anticoagulation. Although clinical sequelae are rare, the high rate of occurrence suggests that alterations in the technique, such as the addition of antiplatelet agents, should be considered.

Adult↗