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Biomedical subjects

R G González

Publications and source records attributed to R G González.

At least 19 recordsLinked to original sources

Imaging-guided acute ischemic stroke therapy: From "time is brain" to "physiology is brain".

The number of potential patients who are actually treated for acute ischemic stroke is disappointingly low, and effective treatments are making a minor impact on this major public health problem. Imaging is not regularly used to identify the ischemic penumbra, a key concept in stroke physiology, though it is capable of doing so in a clinically relevant manner. Evidence is accumulating that identification of the ischemic penumbra and making treatment decisions on the basis of its presence provide substantial benefit to patient outcomes. Moreover, the same studies suggest that an unexpectedly large proportion of patients are suitable for therapy well past the traditional time windows because of the existence of a substantial ischemic penumbra. Modern MR imaging and CT systems, now widely available, are capable of answering the most relevant physiologic questions in acute ischemic stroke. This capability presents new opportunities and responsibilities to neuroradiologists to make appropriate imaging readily available and to have the imaging data rapidly processed and interpreted. In this article, acute ischemic stroke therapy, including the role of imaging in current medical practice, is reviewed, and an evidence-based alternative to contemporary acute ischemic stroke therapy is suggested.

Acute Disease↗

Ischemic stroke: effects of etiology and patient age on the time course of the core apparent diffusion coefficient.

PURPOSE: To determine whether the evolution of the core apparent diffusion coefficient (ADC) of water in ischemic stroke varies with patient age or infarct etiology. MATERIALS AND METHODS: One hundred forty-seven patients with stroke underwent 236 diffusion-weighted magnetic resonance imaging examinations. Etiologies of lesions were classified according to predefined criteria; in 224 images, the diagnosis of lacune could be firmly established or excluded. ADC was measured in the center of each lesion and in contralateral normal-appearing brain. A model was used to describe the time course of relative ADC (rADC), which is calculated by dividing the lesion ADC by the contralateral ADC, and to test for age- or etiology-related differences in this time course. RESULTS: Transition from decreasing to increasing rADC was estimated at 18.5 hours after stroke onset. In subgroup analysis, transition was earlier in nonlacunes than in lacunes (P =.02). There was a trend toward earlier transition in patients older than the median age of 66.0 years, compared with younger patients (P =.06). Pseudonormalization was estimated at 216 hours. Among nonlacunes, the rate of subsequent rADC increase was more rapid in younger patients than in older patients (P =.001). Within the smaller sample of lacunes, however, no significant age-related difference in this rate was found. CONCLUSION: Differences in ADC depending on the patient's age and infarct etiology suggest differing rates of ADC progression.

Adult↗

Early brain injury in the SIV-macaque model of AIDS.

OBJECTIVE: To specify the type and severity of cellular damage in the central nervous system soon after infection and at later stages of disease in the SIV-macaque model of AIDS. DESIGN AND METHODS: Adjacent samples of frontal cortical gray matter were taken from three groups of macaques: uninfected controls (n = 4), acute (14 days post-infection; n = 4), and chronic (mean 2 years post-infection; n = 7). In vitro high resolution magnetic resonance spectroscopy of snap frozen intact tissue and quantitative neuropathology measurements of synaptophysin, calbindin, and glial fibrillary acidic protein (GFAP) in formalin-fixed tissue were performed. RESULTS: Losses in n-acetylaspartate and calbindin (indicating neuronal injury and/or death) and decreases in synaptophysin immunoreactivity (indicating synaptodendritic injury) were detected along with increases in GFAP (indicating reactive gliosis). Cellular injury worsened progressively with increased time after infection. CONCLUSIONS: These results are the first direct evidence that neuronal injury occurs soon after infection. The exacerbation of injury with time suggests a connection between the early response of the central nervous system and dementia, which occurs late in the course of infection. This connection may have broad implications for the study of and the development of therapies for damage of the central nervous system by HIV.

AIDS Dementia Complex↗

Noxious hot and cold stimulation produce common patterns of brain activation in humans: a functional magnetic resonance imaging study.

We used functional magnetic resonance imaging (fMRI) to determine whether similar brain regions activate during noxious hot and cold stimulation. Six male subjects underwent whole brain fMRI during phasic delivery of noxious hot (46 degrees C) and noxious cold (5 degrees C) stimulation to the dorsum of the left hand. Mid-brain regions activated included thalamus, basal ganglia and insula. Cortical areas activated included cingulate, somatosensory, premotor and motor cortices, as well as prefrontal and inferior parietal cortex. Most regions activated bilaterally but with stronger activation contralateral to the stimulus. Noxious cold stimulation produced significantly increased volumes of activation compared to noxious heat in prefrontal areas only. Our results suggest a similar network of regions activate common to the perception of pain produced by either noxious hot or cold stimulation.

Adult↗

Echoplanar chemical shift imaging.

A novel method of chemical shift imaging utilizing echoplanar imaging (EPI) has been developed for the purpose of improving the spatial resolution of metabolite images for the specific goal of high spatial resolution mapping of neuronal content. An EPI sequence was modified to allow temporal offsets of the 180 degree refocusing pulse that encode the chemical shift information into the phase of the signal. Implementation of this method on 1.5 and 3 T human imagers has resulted in images of N-acetyl aspartate in humans with spatial resolution of 360 microl and signal-to-noise ratio approximately 7:1 in less than 13 min.

Aspartic Acid↗

Cytokine mediated regulation of interferon-gamma-induced IDO activation.

Stimulation of human monocyte-derived-macrophages (MDM) with interferon gamma induces the L-tryptophan degrading enzyme indoleamine 2,3-dioxygenase (IDO). It has been well documented that the growth of some intra-cellular parasites such as Chlamydia and Toxoplasma in human fibroblasts and glioblastoma cells is inhibited by IDO mediated L-tryptophan depletion. We have recently shown that IDO induction in cord blood MDM is also responsible for the growth inhibition of extra-cellular group B streptococci and thus for the first time shown an anti-bacterial effect of IDO activation. In view of this immunological function we sought to investigate the regulation, and in particular the downregulation of IDO by the immune system. We describe here the effect of cytokines on IDO activation and in particular the inhibitory function of IL-10, TGF beta and IL-4.

Cytokines↗

Diffusion-weighted MR imaging: diagnostic accuracy in patients imaged within 6 hours of stroke symptom onset.

PURPOSE: To evaluate the diagnostic accuracy of diffusion-weighted magnetic resonance (MR) imaging performed within 6 hours of the onset of stroke symptoms. MATERIALS AND METHODS: The authors reviewed the patient records and images from all patients hospitalized in a 10-month period in whom diffusion-weighted imaging was performed within 6 hours of the onset of strokelike symptoms (n = 22). Analyses included comparison of the initial interpretation of the diffusion-weighted images with the final clinical diagnosis; blinded reviews of computed tomographic (CT) scans and conventional and diffusion-weighted images; and determination of lesion contrast-to-noise ratios (CNRs). RESULTS: Diffusion-weighted images indicated stroke in 14 patients, all of whom had a final diagnosis of acute stroke. Diffusion-weighted images were negative in eight patients, all of whom had a final clinical diagnosis other than stroke (100% sensitivity, 100% specificity, chi 2 = 23.00, P < .0001). Blinded reviews yielded 100% sensitivity and 86% specificity for diffusion-weighted MR imaging (chi 2 = 15.43, P < .0005); 18% sensitivity and 100% specificity for conventional MR imaging (chi 2 = 2.85, P > .2); and 45% sensitivity and 100% specificity for CT (chi 2 = 4.40, P > .10). Lesion percentage CNRs were 77% for diffusion-weighted imaging, 5.5% for CT, 9.8% for T2-weighted MR imaging, and 3.1% for proton-density-weighted MR imaging (P < .002 for diffusion-weighted imaging vs others). CONCLUSION: Diffusion-weighted MR imaging is highly accurate for diagnosing stroke within 6 hours of symptom onset and is superior to CT and conventional MR imaging.

Aged↗

Increased cerebral blood volume in HIV-positive patients detected by functional MRI.

OBJECTIVE: To study changes in cerebral hemodynamics related to HIV infection. BACKGROUND: Cerebral injury is a well-known manifestation of HIV infection. Physiologic changes in the HIV brain may precede structural changes and may be detected by functional MRI (fMRI). METHODS: Dynamic contrast fMRI was used to measure the cerebral blood volume (CBV) in 13 patients infected with HIV and in 7 healthy control subjects. RESULTS: Significant increases in dynamic CBV were found in the deep (p < 0.001) and cortical gray matter (p < 0.05) of HIV-positive (HIV+) patients. Patients with definite cognitive impairment showed significantly greater increases in CBV in the deep gray matter (DGM) compared with those without impairment. In one patient with rapidly progressive cognitive impairment, these abnormalities reversed and paralleled clinical improvement after initiation of zidovudine monotherapy. CONCLUSIONS: This study supports the hypothesis that HIV infection is associated with significant cerebral hemodynamic changes, particularly in the DGM, that may contribute to cognitive dysfunction in AIDS. Functional MRI may be useful for early detection of cerebral injury and for the assessment of novel therapies.

Adult↗

Assessment of cerebral perfusion and arterial anatomy in hyperacute stroke with three-dimensional functional CT: early clinical results.

PURPOSE: Our purpose was to determine the clinical feasibility of quantitative three-dimensional functional CT in patients with hyperacute stroke. METHODS: Twenty-two patients who underwent clinically indicated CT angiography were studied: nine patients had no stroke, eight had mature stroke, and five had hyperacute stroke (less than 3 hours since ictus). Maps were obtained of perfused cerebral blood volume (PBV), and CT angiograms were generated by using standard techniques. RESULTS: Normal PBV values (mean +/- SEM) were 4.6 +/- 0.15% in the gray matter, 1.75 +/- 0.09% in the white matter, 2.91 +/- 0.20% in the cerebellum, 3.18 +/- 0.10% in the caudate, 2.84 +/- 0.23% in the putamen, 2.92 +/- 0.29% in the thalamus, and 1.66 +/- 0.03% in the brain stem. For patients with mature stroke, ischemic changes were visible on noncontrast, contrast-enhanced, and PBV scans. In patients with hyperacute stroke, ischemic changes were either absent or subtle before contrast administration, but became apparent on contrast-enhanced scans. Quantitative PBV maps confirmed reduced regional perfusion. CT angiograms in the hyperacute group showed occlusion of vessels in locations appropriate to the PBV deficits seen. CONCLUSION: Quantitative three-dimensional functional CT is feasible for patients with hyperacute stroke. It is performed by using helical CT techniques, and yields measures of cerebrovascular physiological function, which are useful in this patient population.

Acute Disease↗

Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy.

We describe a method that directly relates tissue neuropathological analysis to medical imaging. Presently, only indirect and often tenuous relationships are made between imaging (such as MRI or x-ray computed tomography) and neuropathology. We present a biochemistry-based, quantitative neuropathological method that can help to precisely quantify information provided by in vivo proton magnetic resonance spectroscopy (1HMRS), an emerging medical imaging technique. This method, high resolution magic angle spinning (HRMAS) 1HMRS, is rapid and requires only small amounts of unprocessed samples. Unlike chemical extraction or other forms of tissue processing, this method analyzes tissue directly, thus minimizing artifacts. We demonstrate the utility of this method by assessing neuronal damage using multiple tissue samples from differently affected brain regions in a case of Pick disease, a human neurodegenerative disorder. Among different regions, we found an excellent correlation between neuronal loss shown by traditional neurohistopathology and decrease of the neuronal marker N-acetylaspartate measured by HRMAS 1HMRS. This result demonstrates for the first time, to our knowledge, a direct, quantitative link between a decrease in N-acetylaspartate and neuronal loss in a human neurodegenerative disease. As a quantitative method, HRMAS 1HMRS has potential applications in experimental and clinical neuropathologic investigations. It should also provide a rational basis for the interpretation of in vivo 1HMRS studies of human neurological disorders.

Amino Acids↗

H. M.'s medial temporal lobe lesion: findings from magnetic resonance imaging.

Although neuropsychological studies of the amnesic patient H. M. provide compelling evidence that normal memory function depends on the medial temporal lobe, the full extent of his surgical resection has not been elucidated. We conducted magnetic resonance imaging studies to specify precisely the extent of his bilateral resection and to document any other brain abnormalities. The MRI studies indicated that the lesion was bilaterally symmetrical and included the medial temporal polar cortex, most of the amygdaloid complex, most or all of the entorhinal cortex, and approximately half of the rostrocaudal extent of the intraventricular portion of the hippocampal formation (dentate gyrus, hippocampus, and subicular complex). The collateral sulcus was visible throughout much of the temporal lobe, indicating that portions of the ventral perirhinal cortex, located on the banks of the sulcus, were spared; the parahippocampal cortex (areas TF and TH) was largely intact. The rostrocaudal extent of the ablation was approximately 5.4 cm (left) and 5.1 cm (right). The caudal 2 cm, approximately, of the hippocampus body (normal length, approximately 4 cm) was intact, although atrophic. The temporal stem was intact. Outside the temporal lobes, the cerebellum demonstrated marked atrophy, and the mammillary nuclei were shrunken. The lateral temporal, frontal, parietal, and occipital lobe cortices appeared normal for age 66 years. The mediodorsal thalamic nuclei showed no obvious radiological changes. These findings reinforce the view that lesions of the hippocampal formation and adjacent cortical structures can produce global and enduring amnesia and can exacerbate amnesia beyond that seen after more selective hippocampal lesions.

Aged↗

1H magnetic resonance spectroscopy reveals neuronal injury in a simian immunodeficiency virus macaque model.

Infection with human immunodeficiency virus (HIV) commonly results in neurologic disease called the AIDS dementia complex. Neuronal loss and injury have been found in the HIV brain, but the underlying mechanisms are not understood. The simian immunodeficiency virus (SIV)-infected macaque is an excellent animal model for HIV infection, but neuronal loss has not been demonstrated. To determine whether neuronal damage occurs in the SIV brain, we quantified the neuronal marker N-acetylaspartate (NAA) using proton magnetic resonance spectroscopy (1H-MRS) in brain extracts of control and SIV-infected macaques and correlated these findings with histologic analyses. We found reduced NAA in the SIV-infected animals compared with controls (2.94 +/- 1.37 versus 6.21 +/- 1.73 micromol/g of wet weight; p = 0.004). A significant decrease in NAA was also found in SIV-infected animals sacrificed in the acute stages of infection 9 or 10 days after inoculation with SIVmacYnef. We conclude that SIV infection of rhesus macaques results in neuronal damage that is demonstrable shortly after infection and that 1H-MRS may be used to measure such injury. The results further support the SIV macaque as a useful model to study the mechanisms of neuropathogenesis by HIV.

Animals↗

The hippocampal formation participates in novel picture encoding: evidence from functional magnetic resonance imaging.

Considerable evidence exists to support the hypothesis that the hippocampus and related medial temporal lobe structures are crucial for the encoding and storage of information in long-term memory. Few human imaging studies, however, have successfully shown signal intensity changes in these areas during encoding or retrieval. Using functional magnetic resonance imaging (fMRI), we studied normal human subjects while they performed a novel picture encoding task. High-speed echo-planar imaging techniques evaluated fMRI signal changes throughout the brain. During the encoding of novel pictures, statistically significant increases in fMRI signal were observed bilaterally in the posterior hippocampal formation and parahippocampal gyrus and in the lingual and fusiform gyri. To our knowledge, this experiment is the first fMRI study to show robust signal changes in the human hippocampal region. It also provides evidence that the encoding of novel, complex pictures depends upon an interaction between ventral cortical regions, specialized for object vision, and the hippocampal formation and parahippocampal gyrus, specialized for long-term memory.

Adult↗

Brain choline-containing compounds are elevated in HIV-positive patients before the onset of AIDS dementia complex: A proton magnetic resonance spectroscopic study.

The CNS is frequently involved in human immunodeficiency virus (HIV) infection. In recent studies using proton magnetic resonance spectroscopy, investigators found a significant reduction in N-acetyl aspartate, a metabolic marker of neurons, in late stages of dementia. To further understand the relationship between proton magnetic resonance spectroscopy changes and clinical disease and dementia, we compared 20 HIV-infected patients presenting at varying stages of acquired immunodeficiency syndrome (AIDS) dementia complex and infection to 10 age-matched controls. We found a significant reduction in N-acetyl aspartate/creatine only in patients who had advanced dementia and CD4 counts less that 200/microliter. By contrast, a significant elevation in compounds containing choline was present in patients in the early stages of HIV infection of who had CD4 counts greater than 200/microliter, in patients with normal MRI scans, and in all AIDS dementia complex groups, including subjects with no or minimal cognitive impairment. An elevated choline level also occurred in later stages of HIV infection (CD4 < 200/microliter). Our results suggest that an increase in choline occurs before N-acetyl aspartate decrements, MRI abnormalities, and the onset of dementia, and may therefore provide a useful marker for early detection of brain injury associated with HIV infection.

AIDS Dementia Complex↗

Quantitative in vivo 1H nuclear magnetic resonance spectroscopic imaging of neuronal loss in rat brain.

The aim of this research was to determine whether in vivo nuclear magnetic resonance spectroscopic measurement of N-acetyl aspartate, a neuron specific brain marker, provides a quantitative index of neuronal loss. Five rats were injected unilaterally in the corpus striatum with kainic acid, an analogue of glutamate that causes excitotoxic degeneration of intrinsic neurons, and were subjected to nuclear magnetic resonance imaging and spectroscopic imaging. Measurements of N-acetyl aspartate were determined in vivo and compared to post mortem nuclear magnetic resonance spectroscopic measures of N-acetyl aspartate and choline acetyl transferase and glutamate decarboxylase activities, biochemical markers for striatal intrinsic neuronal integrity. Mean per cent neuronal survival of hemispheres with lesion versus the contralateral hemispheres measured 72 for glutamate decarboxylase and 71 for N-acetyl aspartate (in vivo), 74 for N-acetyl aspartate (in vitro), and 62 for choline acetyl transferase, respectively. Our studies in rats have shown that estimates of neuronal loss through nuclear magnetic resonance spectroscopic measurements of N-acetyl aspartate are equivalent to traditional neuronal enzyme activity assays. The results unequivocally demonstrate that N-acetyl aspartate is a valid and sensitive neuronal marker with the capability of providing accurate assessments of neuronal loss in vivo.

Animals↗

Functional MR in the evaluation of dementia: correlation of abnormal dynamic cerebral blood volume measurements with changes in cerebral metabolism on positron emission tomography with fludeoxyglucose F 18.

PURPOSE: To determine whether magnetic susceptibility functional MR imaging of cerebral blood volumes provides information similar to fludeoxyglucose F 18 positron emission tomography (PET) brain images in patients undergoing evaluation for dementia. METHODS: Ten subjects were studied with both PET and functional MR. Clinical diagnoses included probable Alzheimer disease (n = 5), possible Alzheimer disease (n = 1), Pick disease (n = 2), and primary progressive aphasia (n = 2). The studies were quantitatively evaluated by coregistration of PET and functional MR images followed by regression analyses of corresponding regions of interest. Qualitatively, each brain was categorized into eight regions, and each was classified as normal or abnormal by visual inspection. RESULTS: Correlation coefficients between registered functional MR and PET images were excellent (mean, r = 0.58) in most of the cerebrum. Significant correlations were observed in 72 of 74 brain sections. Qualitatively, 16 brain regions were judged to be abnormal by both MR imaging and PET; 46 regions were normal by both; 10 regions were abnormal by PET only; and 8 regions were abnormal only by functional MR. The concordance between functional MR and PET was 78%, which was highly significant. CONCLUSION: Cerebral blood volumes images derived from magnetic susceptibility (functional MR) provide information similar to fludeoxyglucose F 18 PET images in demented patients undergoing evaluation for dementia.

Aged↗

[Cyst of the ejaculatory duct].

Presentation of a new case of cyst of the ejaculatory duct, diagnosed in a 49-year-old patient. Unspecific symptomatology, with hemospermia and urethrorrhagia of 6 months evolution. Diagnosis is reached by abdominal and transrectal ultrasound and deferent-vesiculography. Computerized Axial Tomography and Magnetic Nuclear Resonance are performed to document the case and for subsequent follow-up. No other associated malformations are found. Following failure of endoscopic surgery, the original approach, abdominal exeresis is performed with excellent evolution both in the immediate post-operative and at 1-year follow-up. Likely etiology and differential diagnosis from other male pelvic cysts are discussed. List of references on differential diagnosis and published cases in included.

Cysts↗

Simultaneous multinuclear magnetic resonance imaging and spectroscopy.

A technique has been developed to perform simultaneous multinuclear magnetic resonance imaging and spatially localized spectroscopy. It is inherently superior in terms of time efficiency over current approaches which use sequential or interleaved methods. The pulse sequence uses a parallel excitation and acquisition scheme to acquire multislice proton images concurrently with phosphorus-31 spectroscopic images. Because the phosphorus signal is necessarily collected in the presence of a gradient, an essential element of the technique is an algorithm to extract pure chemical-shift information.

Algorithms↗