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Biomedical subjects

N Mullani

Publications and source records attributed to N Mullani.

At least 19 recordsLinked to original sources
PubMed2000

Frequency and clinical implications of fluid dynamically significant diffuse coronary artery disease manifest as graded, longitudinal, base-to-apex myocardial perfusion abnormalities by noninvasive positron emission tomography.

BACKGROUND: Diffuse coronary atherosclerosis is the substrate for plaque rupture and coronary events. Therefore, in patients with mild arteriographic coronary artery disease without significant segmental dipyridamole-induced myocardial perfusion defects, we tested the hypothesis that fluid dynamically significant diffuse coronary artery narrowing is frequently manifest as a graded, longitudinal, base-to-apex myocardial perfusion abnormality by noninvasive PET. METHODS AND RESULTS: In this study, 1001 patients with documented coronary artery disease by coronary arteriography showing any visible coronary artery narrowing underwent rest-dipyridamole PET perfusion imaging. Quantitative severity of dipyridamole-induced, circumscribed, segmental PET perfusion defects was objectively measured by automated software as the minimum quadrant average relative activity indicating localized flow limiting stenoses. Quantitative severity of the graded, longitudinal, base-to-apex myocardial perfusion gradient indicating fluid dynamic effects of diffuse coronary artery narrowing was objectively measured by automated software as the spatial slope of relative activity along the cardiac longitudinal axis. CONCLUSIONS: In patients with mild arteriographic disease without statistically significant dipyridamole-induced segmental myocardial perfusion defects caused by flow-limiting stenoses compared with normal control subjects, there was a graded, longitudinal, base-to-apex myocardial perfusion gradient significantly different from normal control subjects (P=0. 001) that was also observed for moderate to severe dipyridamole-induced segmental perfusion defects (P=0.0001), indicating diffuse disease underlying segmental perfusion defects; 43% of patients with or without segmental perfusion defects demonstrated graded, longitudinal, base-to-apex perfusion abnormalities beyond +/-2 SD of normal control subjects, indicating diffuse coronary arterial narrowing by noninvasive PET perfusion imaging.

Adult↗
PubMed2000

9:45-10:00. Superimposition of EBCT Determined Coronary Calcium Deposits onto Myocardial PET Perfusion Images by Rubidium-82 and Nitrogen-13 Ammonia for Assessment of Flow Limiting Defects.

Calcium localization by Electron Beam CT (EBCT) in the coronary arteries is becoming an important non-invasive method for screening asymptomatic patients for early coronary atherosclerosis. However, the relationship between coronary artery calcium deposits and myocardial perfusion abnormalities has not been established. We have developed software to superimpose location of coronary calcium by EBCT onto PET myocardial perfusion images, so that we can determine the role of location and amount of calcium in the arteries to flow-limiting perfusion defects by PET.EBCT and PET transaxial images are each first converted to three-dimensional arrays of 1 mm voxels. The resulting two image volumes sets are displayed so that a vertical line can be drawn from the clavicle to the spine for proper rotation of the body. The rotated images are then displayed superimposed and are shifted in the vertical, horizontal, and the long axis directions to co-register the EBCT and PET images. The EBCT images are windowed for calcium Houndsfield numbers and calcium location is added to the PET images as a maximum intensity value in the image. The modified PET image volume is then translated back to the PET data format and reprocessed using cardiac analysis software such that the calcium location is superimposed on the PET myocardial perfusion images.Preliminary results of the PET-EBCT superimposition program correlate with location of coronary calcium by EBCT and PET perfusion defects following stress. This technique may be useful for identifying flow-limiting calcium deposits in the coronary arteries.

Journal Article↗
PubMed2000

9:00-9:15. Antiangiogenic Treatment with Endostatin Results in Uncoupling of Blood Flow and Glucose Metabolism in Human Tumors.

Endostatin is a novel antiangiogenic agent currently in phase I trials. In the context of this trial, we are evaluating the use of non-invasive imaging with PET to determine the relationship between tumor blood flow and glucose metabolism in imaged tumors from treated patients.Ten patients have been treated with escalating daily iv Endostatin doses of 30 to 180 mg/m(2). PET images were obtained before the start of therapy and again after 28 days of treatment. Each patient was scanned with Oxygen-15 labeled water for estimation of tumor blood flow and Flourine-18 labeled FDG to estimate tumor metabolic activity. In most cases, two distinct tumor-bearing sites were analyzed in each patient. Thus, a total of 19 tumors were imaged. Regional blood flow and standard uptake values (SUV) were computed at baseline and 28 days post treatment and the percentage change in blood flow and SUV plotted as a function of Endostatin dose.Both blood flow and glucose metabolism in the imaged tumors were observed to increase in patients treated with </=60 mg/m(2)/d, but became uncoupled in the tumors imaged from patients treated at the 180 mg/m(2)/d dose level. Thus, in patients receiving Endostatin at a dose of 180 mg/m(2)/d, blood flow decreased but glucose metabolism increased. This relationship is displayed in Figure 1 below.

Journal Article↗
PubMed2000

9:30-9:45. First Pass FDG Measured Blood Flow in Tumors: A Comparison with O-15 Labeled Water Measured Blood Flow.

The purpose of this study was to determine if the first-pass of FDG can be used to measure regional blood flow in tumors in the absence of perfusion imaging with a known blood flow tracer.PET scans were obtained in patients being evaluated for tumor perfusion and metabolism in a Phase I dose escalating protocol for Endostatin, a novel antiangiogenic agent. A two minutes perfusion scan was done with a bolus injection of 60 mCi of O-15 labeled water followed by a 10 mCi dose of FDG and four sequential scans consisting of a first pass two minutes scan and three 15 minutes scans. Regions of interest were drawn on two tumor sites for each scan. Blood flow was computed using a one-compartment model previously published by the authors. Linear regression analysis was carried out between the first pass FDG measured blood flow and O-15 measured blood flow (Figure 1).Blood flow estimated from the first pass of FDG was linearly correlated with O-15 measured blood flow with an intercept of 0.01, slope of 0.86, and r squared regression coefficient of 0.74 (R = 0.86) for blood flow values of up to 0.6 ml/min/gm of tissue. These results suggests that in the absence of a perfusion tracer, the first pass of FDG provides an estimate of perfusion in a tumor within the limitations of incomplete extraction of FDG compared to O-15 water.

Journal Article↗
PubMed1998

Simple and Patlak models for myocardial blood flow measurements with nitrogen-13-ammonia and PET in humans.

UNLABELLED: The Simple and Patlak models for estimating myocardial blood flow with 13N-ammonia have become attractive for clinical applications with PET because of their simplicity and ease of implementation. However, these models are sensitive to factors such as the data acquisition times and data integration times, which can cause errors in the estimation of myocardial blood flow, as demonstrated in this study. Limiting the application of these models to specific conditions can minimize the errors. METHODS: Dynamic PET images of the uptake of 13N-ammonia in the heart were obtained in seven humans under rest and dipyridamole stress. Myocardial blood flow was estimated using the Simple and Patlak models for different data acquisition times and data integration times. Blood flow values were compared to flow values computed with the two-compartment model as a reference. RESULTS: Blood flow values calculated with the Simple and Patlak models during the first 2 min of data acquisition were closely correlated to the two-compartment model values. Longer acquisition times resulted in significant underestimation of blood flow for the Simple model. Long integration times of greater than 60 sec also resulted in significant underestimation of blood flow for both models. CONCLUSION: The Simple and Patlak models produce estimates of myocardial blood flow that are well correlated with the two-compartment model estimated blood flows for the integration time of 60 sec from 60 to 120 sec postinjection. Because of the errors associated with longer data acquisition times and longer integration times, use of these models should be limited to a well-documented data acquisition paradigm.

Ammonia↗
PubMed1996

Brain glucose metabolism in chronic marijuana users at baseline and during marijuana intoxication.

Despite the widespread abuse of marijuana, knowledge about its effects in the human brain is limited. Brain glucose metabolism with and without delta 9 tetrahydrocannabinol (THC) (main psychoactive component of marijuana) was evaluated in eight normal subjects and eight chronic marijuana abusers with positron emission tomography. At baseline, marijuana abusers showed lower relative cerebellar metabolism than normal subjects. THC increased relative cerebellar metabolism in all subjects, but only abusers showed increases in orbitofrontal cortex, prefrontal cortex, and basal ganglia. Cerebellar metabolism during THC intoxication was significantly correlated with the subjective sense of intoxication. The decreased cerebellar metabolism in marijuana abusers at baseline could account for the motor deficits previously reported in these subjects. The activation of orbitofrontal cortex and basal ganglia by THC in the abusers but not in the normal subjects could underlie one of the mechanisms leading to the drive and the compulsion to self-administer the drug observed in addicted individuals.

Basal Ganglia↗
PubMed1996

Coronary flow and flow reserve by PET simplified for clinical applications using rubidium-82 or nitrogen-13-ammonia.

UNLABELLED: To validate routine, noninvasive determination of absolute myocardial perfusion and coronary flow reserve (CFR), cardiac PET was performed in animals using a simplified imaging protocol, high-dose dipyridamole and a simplified quantitative algorithm specific for 82Rb and 13N-ammonia. METHODS: One hundred thirty-five PET scans were obtained in eight dogs after intravenous 13N-ammonia or 82Rb using serial dynamic PET or a simple two-image dataset. A simple flow model using the two-image dataset was developed for each radionuclide to account for varying arterial input function, flow-dependent myocardial extraction and increased permeability surface area (PS) product due to capillary recruitment at high flows not incorporated into previous models. Myocardial perfusion by the simple model was compared to standard, complete, two-compartment kinetic models validated by comparison to electromagnetic flow meter. RESULTS: For 13N-ammonia, myocardial perfusion by the simple PET model correlated with that by complete compartmental analysis of multiple serial PET images with r = 0.94, slope = 0.96; CFR by compartmental analysis correlated with CFR by electromagnetic flow meter with r = 0.94, slope = 0.97. For 82Rb, myocardial perfusion determined by the simple model correlated with that determined by complete compartmental analysis of multiple serial PET images with r = 0.98, slope = 1.06; CFR determined by compartmental analysis correlated with CFR by electromagnetic flow meter with r = 0.88, slope = 1.13. CONCLUSION: A simplified PET protocol using 13N-ammonia or 82Rb and simple flow models provide noninvasive measurement of CFR up to six times baseline flow throughout the heart and diagnostic image quality for routine clinical application.

Ammonia↗
PubMed1995

Brain glucose metabolism in violent psychiatric patients: a preliminary study.

Positron emission tomography with 18F-deoxyglucose was used to evaluate regional brain glucose metabolism in eight normal subjects and eight psychiatric patients with a history of repetitive violent behavior. Seven of the patients showed widespread areas of low brain metabolism. Although the location of the abnormal regions varied among patients, they showed significantly lower relative metabolic values in medial temporal and prefrontal cortices than did normal comparison subjects. These regions have been implicated as substrates for aggression and impulsivity, and their dysfunction may have contributed to the patients' violent behavior.

Adult↗
PubMed1995

Changes in myocardial perfusion abnormalities by positron emission tomography after long-term, intense risk factor modification.

OBJECTIVE: To quantify changes in size and severity of myocardial perfusion abnormalities by positron emission tomography (PET) in patients with coronary artery disease after 5 years of risk factor modification. DESIGN: Randomized controlled trial. SETTING: Outpatient community setting. INTERVENTION: Randomization of patients to risk factor modification consisting of very low-fat vegetarian diet, mild to moderate exercise, stress management, and group support (experimental group, n = 20) or to usual care by their own physicians, consisting principally of antianginal therapy (control group, n = 15). MAIN OUTCOME MEASURES: Quantitative coronary arteriography and PET at baseline and 5 years after randomization. Automated, objective measures of size and severity of perfusion abnormalities on rest-dipyridamole PET images and of stenosis severity on arteriograms were made by computer algorithms. RESULTS: Size and severity of perfusion abnormalities on dipyridamole PET images decreased (improved) after risk factor modification in the experimental group compared with an increase (worsening) of size and severity in controls. The percentage of left ventricle perfusion abnormalities outside 2.5 SDs of those of normal persons (based on 20 disease-free individuals) on the dipyridamole PET image of normalized counts worsened in controls (mean +/- SE, + 10.3% +/- 5.6%) and improved in the experimental group (mean +/- SE, -5.1% +/- 4.8%) (P = .02); the percentage of left ventricle with activity less than 60% of the maximum activity on the dipyridamole PET image of normalized counts worsened in controls (+13.5% +/- 3.8%) and improved in the experimental group (-4.2% +/- 3.8%) (P = .002); and the myocardial quadrant on the PET image with the lowest average activity expressed as a percentage of maximum activity worsened in controls (-8.8% +/- 2.3%) and improved in the experimental group (+4.9% +/- 3.3%) (P = .001). The size and severity of perfusion abnormalities on resting PET images were also significantly improved in the experimental group as compared with controls. The relative magnitude of changes in size and severity of PET perfusion abnormalities was comparable to or greater than the magnitude of changes in percent diameter stenosis, absolute stenosis lumen area, or stenosis flow reserve documented by quantitative coronary arteriography. CONCLUSIONS: Modest regression of coronary artery stenoses after risk factor modification is associated with decreased size and severity of perfusion abnormalities on rest-dipyridamole PET images. Progression or regression of coronary artery disease can be followed noninvasively by dipyridamole PET reflecting the integrated flow capacity of the entire coronary arterial circulation.

Adult↗
PubMed1995

PET and SPECT imaging for stereotactic localization.

Stereotactic localization using PET and SPECT has been used together with the Leksell stereotactic frame and the other imaging tools routinely provided to Gamma Knife radiosurgery sites. The accuracy of the measurements has been confirmed with CT and MR using a Radiation Analog Dosimetry phantom. The activity of the radionuclide solution placed in the tubes of Elekta Radiosurgery's MR imaging box is somewhat critical because the window levels chosen for the scan will affect the apparent size of the lesion. A technique is presented to resolve areas of activity more than about 12-14 mm apart, and it may prove useful in targeting epileptogenic sites in patients with medically intractable epilepsy.

Humans↗
PubMed1991

Cerebellar metabolic activation by delta-9-tetrahydro-cannabinol in human brain: a study with positron emission tomography and 18F-2-fluoro-2-deoxyglucose.

We investigated the effects of acute i.v. administration of 2 mg of delta 9-tetrahydrocannabinol (THC) on regional brain glucose metabolism using 18F-2-fluoro-2-deoxyglucose and positron emission tomography (PET) in eight normal subjects. Subjects were tested twice: during baseline conditions and 30-40 min after THC administration. Changes in global cerebral glucose metabolism in response to THC were variable: three subjects showed an increase, three showed a decrease, and two showed no change. In contrast, all subjects showed an increase in normalized metabolism in the cerebellum following THC administration. Cerebellar changes were the only significant regional metabolic changes due to THC administration. The increase in metabolic activity in the cerebellum was correlated with the subjective sense of THC intoxication and with plasma THC concentration. Cerebellar localization of metabolic effects due to THC administration corresponds well with the high density of cannabinoid receptors known to be in this area.

Adult↗
PubMed1991

Myocardial metabolism of fluorodeoxyglucose compared to cell membrane integrity for the potassium analogue rubidium-82 for assessing infarct size in man by PET.

Potassium loss from damaged myocardial cells is linearly related to CPK enzyme loss reflecting extent of necrosis. The potassium analog, rubidium-82 (82Rb), is extracted after i.v. injection and retained in viable myocardium but is not trapped or washed out of necrotic regions. To compare myocardial cell metabolism with membrane dysfunction as indicators of necrosis/viability, 43 patients with evolving myocardial infarction and coronary arteriography had positron emission tomography using fluorodeoxyglucose (FDG) and the potassium analog 82Rb. Percent of heart showing FDG defects and 82Rb washout on sequential images indicating failure to retain the potassium analogue were visually assessed and quantified by automated software. Infarct size based on rubidium kinetics correlated closely with size and location on FDG images (visual r = 0.93, automated r = 0.82), suggesting that loss of cell membrane integrity for trapping the potassium analog 82Rb parallels loss of intracellular glucose metabolism, both comparable quantitative markers of myocardial necrosis/viability.

Carbohydrates↗
PubMed1991

Sensitivity of measurements of regional brain activation with oxygen-15-water and PET to time of stimulation and period of image reconstruction.

Measurement of oxygen-15- (15O) water uptake with positron emission tomography (PET) is a sensitive technique to monitor regional brain activation secondary to stimulation paradigms. In order to investigate data acquisition times that show maximal changes in regional activation and to assess the optimal time for stimulus presentation, we investigated 10 controls with 15O-water and PET during baseline and stroboscopic light stimulation. Sequential scans were done varying the time of stimulus presentation. The images were reconstructed using three different periods of data acquisition: uptake phase (initial 30-35 sec), washout phase (40 sec following peak activity in brain), and total activity (3 min). The images reconstructed during the uptake phase showed the largest changes in occipital cortex from stimulation. Maximal changes in occipital cortex were obtained when the visual stimulus was maintained during the uptake phase only.

Adult↗
PubMed1989

Automated quantitation of three-dimensional cardiac positron emission tomography for routine clinical use.

Visual comparison of rest/stress cardiac positron emission tomography indicates coronary flow reserve for diagnosing and assessing severity of coronary artery disease. An accurate, rapid, automated method for comparison and quantitation of paired cardiac PET studies has been developed to analyze size, intensity, statistical significance of and changes in perfusion or metabolism. The method utilizes polar coordinate maps derived from circumferential profiles of true short axis slices; from the short axis data algorithms determine mean and minimum activity levels in the anterior, septal, lateral, inferior and apical regions of the myocardium, percent of the cardiac image in specific ranges of activity levels or their changes and the percent of myocardium beyond 1.5, 2.0, and 2.5 standard deviations from the normal range with blackout display of the areas beyond these statistical limits for rest, stress, and stress/rest ratio polar maps. Additional applications include comparing stress-stress images to evaluate progression/regression of stenoses, early and late resting rubidium images for determining myocardial viability based on rubidium washout kinetics, and perfusion-metabolic comparisons for quantifying ischemia, viability and necrosis after acute myocardial infarction.

Algorithms↗
PubMed1988

Effects of acute alcohol intoxication on cerebral blood flow measured with PET.

Regional distribution of cerebral blood flow was assessed in a group of 13 normal social drinkers under baseline conditions and after acute alcohol intoxication. Blood flow measurements were done using 15O-labeled water and positron emission tomography (PET). Each subject underwent two control sessions under baseline conditions and two sessions after alcohol. Seven of the subjects were given 0.5 g/kg of alcohol and six were given 1 g/kg of alcohol p.o. The first and second post-alcohol scans were done 40 and 60 min after alcohol ingestion. The studies revealed that both the high and the low doses of alcohol reduced blood flow to the cerebellum. This effect was significant only for the high doses of alcohol, which also increased blood flow to the right temporal and the prefrontal cortex. The decrease in blood flow of the cerebellum could account for the muscular incoordination induced by alcohol.

Adult↗
PubMed1988

Cerebral blood flow in chronic cocaine users: a study with positron emission tomography.

Occurrence of cerebrovascular accidents has been associated with cocaine abuse. We investigated the relative distribution of cerebral blood flow (CBF) in groups of chronic cocaine users, and of normal controls. Relative CBF was measured using positron emission tomography and 15 oxygen-labelled water. The cocaine users showed areas of deranged CBF as evidenced by patchy regions of defective isotope accumulation throughout their brain. The chronic cocaine users showed decreased relative CBF in the prefrontal cortex when compared with normal subjects. The repeated scans of some cocaine users, after 10 days of cocaine withdrawal, continued to show decreased relative CBF of the prefrontal cortex. We hypothesise that some of the widespread defects in CBF in the cocaine users could reflect the effects of vasospasm in cerebral arteries exposed chronically to the sympathomimetic actions of cocaine.

Adult↗
PubMed1988

Cerebral involvement in systemic lupus erythematosus.

Four patients with central nervous system lupus erythematosus (SLE), were studied with nuclear magnetic resonance imaging (NMRI) and positron emission tomography (PET) to assess cerebral blood flow and glucose metabolism. The NMRI showed brain atrophy and demyelinating defects. The PET scan showed cerebral blood flow and metabolic abnormalities that improved in one patient after neuropsychiatric recovery. These preliminary findings demonstrate cerebral derangements in patients with SLE cerebritis.

Adult↗