Biomedical subjects

Jeffry R Alger

Publications and source records attributed to Jeffry R Alger.

13 recordsLinked to original sources

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↗

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↗

PubMed2002

Late secondary ischemic injury in patients receiving intraarterial thrombolysis.

Although animal models have demonstrated that late secondary cerebral injury after arterial occlusion and subsequent recanalization may limit the benefit of reperfusion therapy, this phenomenon has not been well characterized in humans. Diffusion-perfusion magnetic resonance imaging studies were performed before treatment, early after treatment, and at day 7 in patients undergoing vessel recanalization with intraarterial thrombolytics. Among 18 patients studied, mean age was 71 (range, 27-94), and median entry National Institutes of Health Stroke Scale score was 13 (range, 6-25). Early after recanalization, partial or complete normalization of diffusion imaging abnormalities occurred in 8 of 18 (44%) patients. Among the eight patients with early diffusion imaging reversal, late secondary injury by day 7 occurred in 5 (63%), and sustained normalization of all reversed tissue occurred in 3 (38%). Pretreatment apparent diffusion coefficient values were lowest in regions experiencing no reversal (mean apparent diffusion coefficient, 608 microm(2)/sec), intermediate in regions with reversal and secondary decline (617 microm(2)/sec), and highest in regions with sustained reversal (663 microm(2)/sec). There was a trend toward less improvement in neurological deficit in patients with secondary injury versus patients with sustained reversal. In the future, late secondary tissue injury may become an important therapeutic target for postreperfusion neuroprotective therapies, with treatment efficacy monitored by serial diffusion magnetic resonance imaging.

Adult↗

PubMed2002

Novel methodology for the archiving and interactive reading of clinical magnetic resonance spectroscopic imaging.

Archiving clinical magnetic resonance spectroscopic imaging (MRSI) data and presenting the data to specialists (e.g., neuroradiologists, neurosurgeons, neurologists, neuro-oncologists, and MR scientists) who work in different physical locations is a practical problem of significance. This communication describes a novel solution. The study hypothesis was that it is possible to use widely available distributed computing techniques to create a clinical MRSI user interface addressable from any personal computer with a suitable network connection. A worldwide web MRSI archive and interface system was created that permits the user to interactively view individual MRSI voxel spectra with correlation to MR images and to parametric spectroscopic images. Web browser software (i.e., Netscape and Internet Explorer) permits users in various physical locations to access centrally archived MRSI data using a variety of operating systems and client workstations. The system was used for archiving and displaying more than 1000 clinical MRSI studies performed at the authors' institution. The system also permits MRSI data to be viewed via the Internet from distant locations worldwide. The study illustrates that widely available software operating within highly distributed electronic networks can be used for archiving and interactive reading of large amounts of clinical MRSI data.

Humans↗

PubMed2002

Brain responses associated with the Valsalva maneuver revealed by functional magnetic resonance imaging.

The Valsalva maneuver, a test frequently used to evaluate autonomic function, recruits discrete neural sites. The time courses of neural recruitment relative to accompanying cardiovascular and breathing patterns are unknown. We examined functional magnetic resonance imaging signal changes within the brain to repeated Valsalva maneuvers and correlated these changes with physiological trends. In 12 healthy subjects (age, 30-58 yr), a series of 25 volumes (20 gradient echo echo-planar image slices per volume) was collected using a 1.5-Tesla scanner during a 60-s baseline and 90-s challenge period consisting of three Valsalva maneuvers. Regions of interest were examined for signal intensity changes over baseline and challenge conditions in cardiorespiratory-related regions. In addition, whole brain correlations between signal intensity and heart rate and airway load pressure were performed on a voxel-by-voxel basis. Significant signal changes, correlated with the time course of load pressure and heart rate, emerged within multiple areas, including the amygdala and hippocampus, insular and lateral frontal cortices, dorsal pons, dorsal medulla, lentiform nucleus, and fastigial and dentate nuclei of the cerebellum. Signal intensities peaked early in the Valsalva maneuver within the hippocampus and amygdala, later within the dorsal medulla, pons and midbrain, and deep cerebellar nuclei, and last within the lentiform nuclei and the lateral prefrontal cortex. The ventral pontine signals increased during the challenge, but not in a fashion correlated to load pressure or heart rate. Sites showing little or no correlation included the vermis and medial prefrontal cortex. These data suggest an initiating component arising in rostral brain areas, a later contribution from cerebellar nuclei, basal ganglia, and lateral prefrontal cortex, and a role for the ventral pons in mediating longer term processes.

Adult↗

PubMed2002

Magnetic resonance imaging detection of microbleeds before thrombolysis: an emerging application.

BACKGROUND: Hemorrhagic transformation (HT) is a major complication of thrombolytic treatment for acute ischemic stroke. Although a history of prior intracerebral hemorrhage diagnosed by head CT is a contraindication to thrombolysis, there are no guidelines or data regarding evidence of prior asymptomatic microbleeds visualized with T2*-weighted magnetic resonance imaging (MRI). METHODS: Pretreatment T2*-weighted MRI sequences were retrospectively analyzed in all patients receiving intra-arterial thrombolytic therapy and undergoing a pretreatment MRI at our institution. The frequency and location of prior microbleeds was determined and compared with the frequency and location of secondary HT after therapy. RESULTS: Five of 41 patients undergoing MRI before receiving intra-arterial thrombolytic therapy demonstrated evidence of prior microbleeds on the pretreatment MRI studies. Major symptomatic hemorrhage occurred in 1 of 5 patients with microbleeds compared with 4 of 36 patients without. Only 1 patient in the entire 41-patient cohort experienced any HT outside the acute ischemic field. In this patient, the symptomatic hemorrhage occurred directly at the site of a prior microbleed, contralateral to the acute ischemic event. CONCLUSIONS: Old silent microbleeds, visualized with T2*-weighted MRI sequences, may be a marker of increased risk of HT in patients receiving thrombolytic therapy for acute ischemic stroke. Pretreatment screening of thrombolytic candidates with these MRI sequences may be useful in the future to identify these patients.

Acute Disease↗