Biomedical subjects

Jeffry R Alger

Publications and source records attributed to Jeffry R Alger.

At least 19 recordsLinked to original sources

PubMed2006

Predictors of cerebral microbleeds in acute ischemic stroke and TIA patients.

BACKGROUND: Cerebral microbleeds (CMB) detected on gradient-echo T2*-weighted MRI have been associated with cognitive impairment and the potential for increased risk of intracranial hemorrhage. We evaluated risk factors for these microangiopathic lesions in a cohort of stroke and transient ischemic attack patients. METHODS: Presence and number of CMB in consecutive acute stroke patients admitted to a university hospital stroke service over an 18-month period were rated. Multivariate models were generated to determine the contribution of 21 demographic and clinical variables to the frequency and number of CMB. RESULTS: Of 164 patients (mean age 71 years, 52% female), 57 (35%) had CMB evident on gradient-echo T2*-weighted MRI. CMB were more commonly noted among patients with small vessel disease ischemic stroke mechanism (47%) than large vessel atherothromboembolic (12%) or cardioembolic (18%, p = 0.0001). In univariate analysis, patients with CMB were older, (p = 0.008), more likely to have been on >1 antihypertensive prior to admission (p = 0.024) than those without CMB. In multivariate logistic regression analyses, presumed small vessel stroke subtype, history of atrial fibrillation, being on >1 antihypertensive prior to admission, and smoking were independent factors increasing the risk of CMB. Logistic regression analysis by number of CMB showed almost similar findings. CONCLUSIONS: CMB are more frequently noted in hospitalized stroke and transient ischemic attack patients with small vessel ischemia, as well as those with important modifiable vascular risk factors like atrial fibrillation and smoking.

Adult↗

PubMed2006

MRI measurement of the uptake and retention of motexafin gadolinium in glioblastoma multiforme and uninvolved normal human brain.

PURPOSE: Motexafin gadolinium (MGd) is an investigational pharmaceutical with radiation enhancing properties. Magnetic Resonance Imaging (MRI) was used to measure brain and tumor MGd levels to evaluate (1) the degree to which MGd passes through the intact blood brain barrier, and (2) the retention of MGd in tumor in patients with glioblastoma multiforme (GBM). METHODS AND MATERIALS: MRI studies were performed on GBM patients who participated in a phase I clinical trial in which MGd was given during standard fractionated radiation therapy. MGd was administered daily (Monday to Friday) for five or 10 doses as a loading regimen, followed by three times per week dosing as a maintenance schedule. T1-weighted MRI was performed at intervals throughout the course of the MGd administration and radiation therapy in the 33 participating patients. Eleven patients had pre- and post-MGd scans, allowing for study of MGd's normal blood brain barrier penetration. Twenty-two patients had adequate residual tumor for measurements to evaluate MGd retention in tumor during the course of MGd and radiation administration. RESULTS AND CONCLUSIONS: The studies of uninvolved brain tissue support the conclusion that MGd does not cross the intact blood brain barrier in detectable quantities. The tumor study showed MGd uptake during loading and maintenance without measurably significant fall off on non-dosage days during the maintenance dosing. Although the number of cases is small, the 10-day loading regimen showed greater drug loading and retention compared with the 5 days loading regimen.

Antineoplastic Agents↗

PubMed2006

Elevated mean diffusivity in widespread brain regions in congenital central hypoventilation syndrome.

PURPOSE: To investigate whether mean diffusivity (MD) values are altered in brain areas underlying cardiovascular and respiratory control in congenital central hypoventilation syndrome (CCHS). MATERIALS AND METHODS: Conventional and diffusion tensor imaging were performed in 15 CCHS and 30 control subjects, using a 3.0-Tesla MRI unit. Mean diffusivity maps were calculated from diffusion-weighted images, spatially normalized, smoothed, and compared between groups using analysis of covariance at each voxel with age as covariate. Global mean MD values of gray and white matter were determined in individual subjects and compared between groups and with age. RESULTS: Increased MD values appeared in CCHS over control subjects within multiple areas influencing breathing and cardiovascular control, including the midbrain, pons, and dorsal and ventral medulla. Other altered sites included cerebellar cortex and deep nuclei, basal ganglia, basal forebrain, and temporal and frontal cortices. Global mean MD values for gray and white matter did not differ between groups; however, gray matter MD values significantly increased with age (P < 0.02) in CCHS patients only. CONCLUSION: Increased MD values suggest regional alterations or injury; affected areas include brainstem sites classically associated with autonomic and respiratory control. Other altered regions mediate additional physiological characteristics impaired in CCHS.

Adolescent↗

PubMed2005

Neuroanatomic deficits in congenital central hypoventilation syndrome.

Congenital Central Hypoventilation Syndrome (CCHS) patients exhibit compromised autonomic regulation, reduced breathing drive during sleep, diminished ventilatory responses to chemoreceptor stimulation, and diminished air hunger perception. The syndrome provides an opportunity to partition neural processes regulating breathing and cardiovascular action. No obvious lesions appear with conventional magnetic resonance imaging; however, T2 relaxometry procedures can detect reduced cell or fiber density or diminished myelination not found with routine evaluation. High-resolution T1, proton density, and T2-weighted brain images were collected from 12 patients and 28 age- and gender-matched controls. Voxel-by-voxel T2 maps were generated from the proton density and T2-weighted images and evaluated by voxel-based-relaxometry procedures. Normalized and smoothed T2 maps were compared between groups using analysis of covariance at each voxel, with age and ventricle size included as covariates. Patients showed damaged or maldeveloped tissue, principally right-sided, including white matter from the level of the anterior cingulate cortex caudally to the level of the posterior cingulate and laterally to the posterior superior temporal cortex. Portions of the posterior, mid, and anterior cingulate, as well as the internal capsule, putamen, and globus pallidus and basal forebrain extending to the anterior and medial thalamus were affected. Deficits in the cingulum bundle and mid-hippocampus and ventral prefrontal cortex appeared, as well as the right cerebellar cortex and deep nuclei. Neuroanatomic deficiencies in limbic structures suggest a structural basis for reduced air hunger perception, thermoregulatory and autonomic deficiencies in the syndrome, while cerebellar deficits may also contribute to breathing and cardiovascular dysregulation.

Adolescent↗

PubMed2005

Inspiratory loading elicits aberrant fMRI signal changes in obstructive sleep apnea.

We hypothesized that neural processes mediating deficient sensory and autonomic regulatory mechanisms in obstructive sleep apnea (OSA) would be revealed by responses to inspiratory loading in brain regions regulating sensory and motor control. Functional magnetic resonance imaging (fMRI) signals and physiologic changes were assessed during baseline and inspiratory loading in 7 OSA patients and 11 controls, all male and medication-free. Heart rate increases to inspiratory loading began earlier and load pressures were achieved later in OSA patients. Comparable fMRI changes emerged in multiple brain regions in both groups, including limbic, cerebellar, midbrain, and primary motor cortex. However, in OSA subjects, altered signals appeared in primary sensory thalamus and sensory cortex, supplementary motor cortex, cerebellar cortex and deep nuclei, cingulate, medial temporal, and insular cortices, right hippocampus, and midbrain. Signal delays occurred in basal ganglia. We conclude that areas mediating sensory and autonomic processes, and motor timing, are affected in OSA; many of these areas overlap regions of previously demonstrated gray matter loss.

Adult↗

PubMed2004

Comparison of MRI and CT for detection of acute intracerebral hemorrhage.

CONTEXT: Noncontrast computed tomography (CT) is the standard brain imaging study for the initial evaluation of patients with acute stroke symptoms. Multimodal magnetic resonance imaging (MRI) has been proposed as an alternative to CT in the emergency stroke setting. However, the accuracy of MRI relative to CT for the detection of hyperacute intracerebral hemorrhage has not been demonstrated. OBJECTIVE: To compare the accuracy of MRI and CT for detection of acute intracerebral hemorrhage in patients presenting with acute focal stroke symptoms. DESIGN, SETTING, AND PATIENTS: A prospective, multicenter study was performed at 2 stroke centers (UCLA Medical Center and Suburban Hospital, Bethesda, Md), between October 2000 and February 2003. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain MRI followed by noncontrast CT. MAIN OUTCOME MEASURES: Acute intracerebral hemorrhage and any intracerebral hemorrhage diagnosed on gradient recalled echo (GRE) MRI and CT scans by a consensus of 4 blinded readers. RESULTS: The study was stopped early, after 200 patients were enrolled, when it became apparent at the time of an unplanned interim analysis that MRI was detecting cases of hemorrhagic transformation not detected by CT. For the diagnosis of any hemorrhage, MRI was positive in 71 patients with CT positive in 29 (P<.001). For the diagnosis of acute hemorrhage, MRI and CT were equivalent (96% concordance). Acute hemorrhage was diagnosed in 25 patients on both MRI and CT. In 4 other patients, acute hemorrhage was present on MRI but not on the corresponding CT--each of these 4 cases was interpreted as hemorrhagic transformation of an ischemic infarct. In 3 patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In 1 patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. In 49 patients, chronic hemorrhage, most often microbleeds, was visualized on MRI but not on CT. CONCLUSION: MRI may be as accurate as CT for the detection of acute hemorrhage in patients presenting with acute focal stroke symptoms and is more accurate than CT for the detection of chronic intracerebral hemorrhage.

Acute Disease↗

PubMed2004

Evolving paradigms in neuroimaging of the ischemic penumbra.

Identification of the ischemic penumbra in the acute stroke clinical setting is an important goal for stroke researchers and clinicians. Various models for imaging the penumbra with MRI have been proposed, including the pioneering diffusion-perfusion mismatch model and later multivariate approaches. A number of multicenter clinical trials are now under way to test these models and confirm the utility of MRI-based treatment decisions. Present knowledge about MRI visualization of the salvageable penumbra suggests a promising future in which MRI studies are performed routinely in the acute stroke setting and the data provided by these MRI studies assist in individualizing therapeutic decisions and identifying effective therapies that can be delivered at late time points.

Brain Ischemia↗

PubMed2004

Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis.

The mechanisms controlling axon guidance are of fundamental importance in understanding brain development. Growing corticospinal and somatosensory axons cross the midline in the medulla to reach their targets and thus form the basis of contralateral motor control and sensory input. The motor and sensory projections appeared uncrossed in patients with horizontal gaze palsy with progressive scoliosis (HGPPS). In patients affected with HGPPS, we identified mutations in the ROBO3 gene, which shares homology with roundabout genes important in axon guidance in developing Drosophila, zebrafish, and mouse. Like its murine homolog Rig1/Robo3, but unlike other Robo proteins, ROBO3 is required for hindbrain axon midline crossing.

Adult↗

PubMed2004

Acute basilar artery occlusion: diffusion-perfusion MRI characterization of tissue salvage in patients receiving intra-arterial stroke therapies.

BACKGROUND AND PURPOSE: Diffusion-perfusion MRI in patients with anterior circulation occlusions has demonstrated salvage of threatened tissue after thrombolytic therapy. Similar studies have not been reported with posterior circulation occlusions. METHODS: Patients with acute basilar artery occlusion treated with intra-arterial thrombolytics were studied with multimodal MRI before treatment, several hours after treatment, and at day 7. RESULTS: Ten patients were studied (9 men, 1 woman). Mean age was 70 years, and median pretreatment National Institutes of Health Stroke Scale (NIHSS) score was 14. In 6 patients imaged before treatment and at day 7, mean pretreatment diffusion-weighted imaging (DWI) lesion volume was 11 cm(3), and day 7, lesion volume was 2.6 cm(3). Significant mismatch was visualized in all 5 patients with pretreatment perfusion-diffusion imaging (mean, 73%; range, 49% to 99%). Late imaging obtained in 4 of these 5 patients demonstrated that mean posttreatment DWI lesion volume (21 cm(3)) was less than the mean initial perfusion lesion volume (62 cm(3)). Although there was no direct correlation between pretreatment DWI volume and initial NIHSS (r=-0.113), there was good correlation between pretreatment perfusion-weighted imaging volume and initial NIHSS (r=0.72). CONCLUSIONS: In this first report of diffusion-perfusion MRI in patients with acute basilar artery occlusions treated with intra-arterial thrombolysis, significant mismatch was visualized on pretreatment studies, suggesting that large volumes of salvageable tissue were present. Final infarct volumes were smaller than pretreatment perfusion volumes, suggesting that substantial volumes of tissue were salvaged by thrombolytic reperfusion.

Acute Disease↗

PubMed2004

Predictors of apparent diffusion coefficient normalization in stroke patients.

BACKGROUND AND PURPOSE: We sought to describe the frequency of normalization of apparent diffusion coefficient (ADC) values that are decreased in hyperacute stroke and to identify characteristics of tissue demonstrating normalization. METHODS: Sixty-eight acute ischemic stroke patients underwent MRI examination (including diffusion/perfusion imaging and MR angiography) within 6 hours (mean, 2.8 hours) after symptom onset, after 24 hours, and again 4 to 7 days later. Lesion volumes with decreased ADC and delayed time to peak in perfusion imaging were determined. In patients showing ADC normalization, volumes with ADC decrease graded as <50%, 50% to 60%, 60% to 70%, and 70% to 80% of the contralateral value were determined by thresholding. Patients were categorized as normalizers (demonstrating ADC normalization in >5 mL tissue with initially decreased ADC) or nonnormalizers (demonstrating ADC normalization in <5 mL tissue). RESULTS: Fourteen patients (19.7%) were classified as normalizers. Eleven of 31 patients (35.5%) initially imaged <3 hours after stroke onset and 3 of 37 (7.5%) of those imaged 3 to 6 hours after onset were normalizers. ADC normalization occurred predominantly in the basal ganglia and white matter after thrombolytic therapy in patients with more distal vessel occlusions. All normalizers demonstrated at least partial tissue reperfusion. Tissue with more severe initial decrease in ADC was less likely to demonstrate normalization. CONCLUSIONS: ADC normalization is not a rare event in acute stroke after tissue reperfusion. Brain tissue with initially decreased ADC, especially within 3 hours after stroke onset, may include "tissue at risk."

Acute Disease↗

PubMed2004

1H MRSI evidence of metabolic abnormalities in childhood-onset schizophrenia.

In adult schizophrenia, magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have revealed volumetric and metabolic defects in multiple brain regions, among them the anterior cingulate, frontal cortex, striatum, thalamus, parietal cortex, and frontal and parietal white matter. This study used proton magnetic resonance spectroscopic imaging ((1)H MRSI) to identify potential metabolic abnormalities in these regions in childhood-onset schizophrenia. (1)H MRSI was acquired at 1.5 T and 272 ms echo time in 11 children and adolescents with schizophrenia (aged 7-18 years; seven boys, four girls; all but two medicated) and 20 age-matched healthy controls (10 boys, 10 girls). Absolute levels of N-acetyl compounds (NAA), creatine plus phosphocreatine (Cr), and choline compounds (Cho) were compared among groups in each region. In schizophrenic patients relative to controls, Cr was 14.3% higher in superior anterior cingulate (mean of left and right hemispheres). Cho was higher in superior anterior cingulate (30.3%), frontal cortex (13.3%), and caudate head (13.5%). In the thalamus, there was also a diagnosis-by-gender interaction, whereby NAA was lower in patients for male but not for female subjects. Elevated Cr suggests abnormal local cell-energy demand and elevated Cho is consistent with a prior proposal that patients with early age-of-onset schizophrenia exhibit phospholipid membrane disturbances. Low NAA may reflect diminished neuronal integrity.

Adolescent↗

PubMed2003

Global BOLD MRI changes to ventilatory challenges in congenital central hypoventilation syndrome.

We evaluated global blood oxygen level dependent (BOLD) signal changes in gray and white matter in 14 congenital central hypoventilation syndrome (CCHS) and 14 control subjects. One baseline image series with room air and three series with 30 s room air followed by 120 s hypercapnia (5% CO2/95% O2), hypoxia (15% O2/85% N2) or hyperoxia (100% O2) were collected. Hypercapnia and hyperoxia raised, and hypoxia lowered gray and white matter global signal in both groups, with smaller changes in white matter. Signal changes in CCHS cases were lower than control subjects for hypercapnia in gray and white matter, slightly more-enhanced in hypoxia, and, except for initial transient responses, were nearly comparable during hyperoxia. Initial signal rate or pattern changes emerged in all three challenges in gray or white matter in control, but not CCHS cases. Neural or vascular mechanisms mediate perfusion differently in CCHS; the aberrant initial transient responses may reflect deficiencies in rapidly-varying physiologic interactions in the syndrome.

Adolescent↗

PubMed2003

Beyond mismatch: evolving paradigms in imaging the ischemic penumbra with multimodal magnetic resonance imaging.

BACKGROUND: The ability to quickly and efficiently identify the ischemic penumbra in the acute stroke clinical setting is an important goal for stroke researchers and clinicians. Early and accurate identification of potentially salvageable versus irreversibly infarcted brain tissue may enable selection of the most appropriate candidates for early stroke therapies and identify patients who may still benefit from late recanalization or neuroprotective treatment. Recent advances in magnetic resonance imaging of the ischemic penumbra have been driven by serial MRI studies characterizing the natural evolution of cerebral infarction as well as the brain's response to reperfusion. SUMMARY OF COMMENT: Based on these studies, various models for imaging the penumbra with MRI have been proposed, including the pioneering diffusion-perfusion mismatch model and later multivariate approaches. Each model has its own unique advantages and disadvantages. CONCLUSIONS: There now are sufficient data to support paradigm shifts in a variety of central tenets regarding MRI and the ischemic penumbra. These include the insights that diffusion-perfusion mismatch does not optimally define the penumbra; that early diffusion lesions are in part reversible and often include both irreversibly infarcted tissue and penumbra; that the visible zone of perfusion abnormality overestimates the penumbra by including regions of benign oligemia; that MRI is a very practical method for acute stroke imaging; and that therapeutic salvage of the ischemic penumbra has been demonstrated in humans using diffusion-perfusion MRI.

Animals↗

PubMed2003

Perfusion-weighted magnetic resonance imaging thresholds identifying core, irreversibly infarcted tissue.

BACKGROUND AND PURPOSE: Identifying core, irreversibly infarcted tissue and salvageable penumbral tissue is crucial to informed, physiologically guided decision making regarding thrombolytic and other interventional therapies in acute ischemic stroke. Pretreatment perfusion MRI offers promise as a means to differentiate core from penumbral tissues. METHODS: Diffusion-perfusion MRIs were performed before treatment and on day 7 in patients undergoing successful vessel recanalization with intra-arterial thrombolytic therapy. Perfusion maps of the time to peak of the residue function (Tmax) were generated after deconvolution of an arterial input function. Initial perfusion abnormalities and final infarct regions were outlined by hand. Posttreatment images were coregistered to the pretreatment study. Voxel-by-voxel and volume analyses were performed to identify thresholds of perfusion abnormalities that best predict core, irreversibly infarcted tissue. RESULTS: Fourteen patients (4 men, 10 women) with vessel recanalization were studied. Mean age was 73 years, and median entry National Institutes of Health Stroke Scale score was 12. Mean time from symptom onset to start of intra-arterial infusion was 245 minutes and to recanalization was 338 minutes. With a voxel-by-voxel analysis, Tmax > or =6 and > or =8 seconds (sensitivity, 71% and 53%; specificity, 63% and 80%) correlated most highly with day 7 final infarct. With a volume analysis, Tmax > or =6 and > or =8 seconds (r2=0.704 and r2=0.705) correlated most highly with day 7 final infarct. CONCLUSIONS: Perfusion-weighted imaging measures of ischemia severity accurately differentiate irreversibly injured core from penumbral, salvageable tissue. The best threshold for identifying core infarcted tissue is adjusted Tmax of > or =6 to 8 seconds.

Acute Disease↗

PubMed2003

fMRI responses to cold pressor challenges in control and obstructive sleep apnea subjects.

Obstructive sleep apnea (OSA) patients exhibit altered sympathetic outflow, which may reveal mechanisms underlying the syndrome. We used functional MRI (fMRI) in 16 control and 10 OSA subjects who were free of cardiovascular or mood-altering drugs to examine neural responses to a forehead cold pressor challenge, which elicits respiratory slowing, bradycardia, and enhanced sympathetic outflow. The magnitude of cold-induced bradycardia was smaller, and respiratory slowing showed greater intersubject variability and reached a nadir later in OSA patients. Both groups showed similar signal changes to cold stimulation in multiple brain sites. However, signal increases emerged in OSA over controls in anterior and posterior cingulate and cerebellar and frontal cortex, whereas signals markedly declined in the ventral thalamus, hippocampus, and insula rather than rising as in controls. Anomalous responses often paralleled changes in breathing and heart rate. Medullary, midbrain areas and lentiform and cerebellar dentate nuclei also showed lower signals in OSA cases. Cold pressor physiological responses are modified in OSA and may result from both diminished and exaggerated responses in multiple brain structures.

Adult↗

PubMed2003

Proton echo-planar spectroscopic imaging with highly effective outer volume suppression using combined presaturation and spatially selective echo dephasing.

A highly effective outer volume suppression (OVS) technique, termed spatially selective echo dephasing (SSED), which employs gradient dephasing of spatially selective spin echoes, is introduced. SSED, which is relatively insensitive to T(1) dispersion among lipid signals and B(1) inhomogeneity, was integrated with very high spatial resolution 2D proton echo-planar spectroscopic imaging (PEPSI) to assess residual lipid bleeding into cortical regions in the human brain. The method was optimized to minimize signal refocusing of secondary spin-echoes in areas of overlapping suppression slices. A comparison of spatial presaturation with single or double SSED, and with combined presaturation and SSED shows that the latter method has superior performance with spatially uniform lipid suppression factors in excess of 70. Metabolite mapping (choline, creatine, and NAA) with a 64 x 64 spatial matrix and 0.3 cm(3) voxels in close proximity to peripheral lipid regions was demonstrated at 1.5 T with a scan time of 32 min using the standard head coil.

Brain↗

PubMed2002

Brain morphology associated with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by repeated occurrences of hypoxic, hypercapnic, and transient blood pressure elevation episodes that may damage or alter neural structures. Underdeveloped structures or pre-existing damage in brain areas may also contribute to the genesis of the syndrome. Brain morphology in 21 patients with OSA and in 21 control subjects was assessed using high-resolution T1-weighted magnetic resonance imaging. Three-dimensional brain images were obtained with voxels of approximately 1 mm3. Images were spatially normalized and segmented into gray matter, white matter, and cerebrospinal fluid. For each segment, regional volumetric differences were determined relative to age, handedness, and group (patients with OSA versus control subjects), using voxel-based morphometry, with OSA effects weighted by disease severity. A significant age effect on total gray matter was found in control subjects but not in patients with OSA. Diminished regional and often unilateral gray matter loss was apparent in multiple sites of the brain in patients with OSA, including the frontal and parietal cortex, temporal lobe, anterior cingulate, hippocampus, and cerebellum. Unilateral loss in well-perfused structures suggests onset of neural deficits early in the OSA syndrome. The gray matter loss occurs within sites involved in motor regulation of the upper airway as well as in areas contributing to cognitive function.

Adult↗

PubMed2002

Neural responses during Valsalva maneuvers in obstructive sleep apnea syndrome.

The repetitive upper airway muscle atonic episodes and cardiovascular sequelae of obstructive sleep apnea (OSA) suggest dysfunction of specific neural sites that integrate afferent airway signals with autonomic and somatic outflow. We determined neural responses to the Valsalva maneuver by using functional magnetic resonance imaging. Images were collected during a baseline and three Valsalva maneuvers in 8 drug-free OSA patients and 15 controls. Multiple cortical, midbrain, pontine, and medullary regions in both groups showed intensity changes correlated to airway pressure. In OSA subjects, the left inferior parietal cortex, superior temporal gyrus, posterior insular cortex, cerebellar cortex, fastigial nucleus, and hippocampus showed attenuated signal changes compared with controls. Enhanced responses emerged in the left lateral precentral gyrus, left anterior cingulate, and superior frontal cortex of OSA patients. The anterior cingulate, cerebellar cortex, and posterior insula exhibited altered response timing patterns between control and OSA subjects. The response patterns in OSA subjects suggest deficits in particular neural pathways that normally mediate the Valsalva maneuver and compensatory actions in other structures.

Adult↗