Cerebral Blood Flow Studies Research Articles

Normalization in PET group comparison studies—The importance of a valid reference region

IntroductionIn positron emission tomography (PET) studies of cerebral blood flow (CBF) and metabolism, the large interindividual variation commonly is minimized by normalization to the global mean prior to statistical analysis. This approach requires that no between-group or between-state differences exist in the normalization region. Given the variability typical of global CBF and the practical limit on sample size, small group differences in global mean easily elude detection, but still bias the comparison, with profound consequences for the physiological interpretation of the results. Materials and methodsQuantitative [15O]H2O PET recordings of CBF were obtained in 45 healthy subjects (21–81 years) and 14 patients with hepatic encephalopathy (HE). With volume-of-interest (VOI) and voxel-based statistics, we conducted regression analyses of CBF as function of age in the healthy group, and compared the HE group to a subset of the controls. We compared absolute CBF values, and CBF normalized to the gray matter (GM) and white matter (WM) means. In additional simulation experiments, we manipulated the cortical values of 12 healthy subjects and compared these to unaltered control data. ResultsIn healthy aging, CBF was shown to be unchanged in WM and central regions. In contrast, with normalization to the GM mean, CBF displayed positive correlation with age in the central regions. Very similar artifactual increases were seen in the HE comparison and also in the simulation experiment. ConclusionRatio normalization to the global mean readily elevates CBF in unchanged regions when a systematic between-group difference exists in gCBF, also when this difference is below the detection threshold. We suggest that the routine normalization to the global mean in earlier studies resulted in spurious interpretations of perturbed CBF. Normalization to central WM yields less biased results in aging and HE and could potentially serve as a normalization reference region in other disorders as well.

A single photon emission computerized tomography (SPECT) study of regional cerebral blood flow in bipolar disorder

A single photon emission computerized tomography (SPECT) study of regional cerebral blood flow in bipolar disorder

Vasospasm probability index: a combination of transcranial Doppler velocities, cerebral blood flow, and clinical risk factors to predict cerebral vasospasm after aneurysmal subarachnoid hemorrhage

The goal in this study was to create an index (vasospasm probability index [VPI]) to improve diagnostic accuracy for vasospasm after subarachnoid hemorrhage (SAH). Seven hundred ninety-five patients in whom aneurysmal SAH was demonstrated by computed tomography, and in whom one or more intracranial aneurysms had been diagnosed, underwent transcranial Doppler (TCD) studies between April 1998 and January 2000. In 154 patients angiography was performed within 24 hours of the TCD examination, and in 75 133Xe cerebral blood flow (CBF) studies were obtained the same day. Seven cases were excluded because of a limited sonographic window. Forty-one women (60.3%) and 27 men (39.7%) between the ages of 35 and 84 years (58.0 +/- 13.2 years [mean +/- standard deviation]) were included. Clinical characteristics analyzed included age, sex, Hunt and Hess grade, Fisher grade, days after SAH, day of treatment, type of treatment (coil embolization, surgical clip occlusion, or conservative treatment), smoking history, and hypertension history. Lindegaard ratios and spasm indexes (TCD velocities/hemispheric CBF) were calculated bilaterally. Digital subtraction angiography images were measured at specific points of interest. Sensitivity, specificity, predictive values, and global accuracy of the different tests were calculated. Logistic regression was used to evaluate the possible predictive factors, and the coefficients of the logistic regression were integrated to create the VPI. In 18 patients (26.5%) symptomatic vasospasm was diagnosed, and 33 (48.5%) had angiographic evidence of vasospasm. For TCD velocities above 120 cm/second at the middle cerebral artery, the global accuracy was 81.1% for the diagnosis of clinical vasospasm and 77.2% for angiographic vasospasm. For a Lindegaard ratio higher than 3.0, the accuracy was 85% for clinical vasospasm and 83.2% for angiographic vasospasm. A spasm index higher than 3.5 had an accuracy of 82.0% for the diagnosis of clinical vasospasm and 81.6% for angiographic vasospasm. The selected model for estimation of clinical vasospasm included Fisher grade, Hunt and Hess grade, and spasm index. The VPI had a global accuracy of 92.9% for clinical vasospasm detection. For diagnosis of angiographic vasospasm, the model included Fisher grade, Hunt and Hess grade, and Lindegaard ratio. The VPI achieved a global accuracy of 89.9% for angiographic vasospasm detection. The use of TCD velocities, Lindegaard ratio, and spasm index independently is of limited value for the diagnosis of clinical and angiographic vasospasm. The combination of predictive factors associated with the development of vasospasm in the new index reported here has a significantly superior accuracy compared with the independent tests and may become a valuable tool for the clinician to evaluate the individual probability of cerebral vasospasm after aneurysmal SAH.

Abstract 2381: Aneurysmal Subarachnoid Hemorrhage: Metabolic and Blood Flow Patterns

Objective: The purpose of this study is to classify and describe the clinically distinct metabolic and hemodynamic phases post-ASAH. Methods: 224 patients who suffered an ASAH (mean age 55±14; 74% female, 26% male) were examined. Patients underwent daily transcranial Doppler (TCD) and cerebral blood flow (CBF) studies (using 133 Xe clearance). Due to the paucity of data on post-hemorrhage day (PHD) 0, the internal carotid artery end-diastolic (ICA ED ) velocity, a surrogate for CBF, was used for the first 24 hours. The brain arteriovenous oxygen difference (AVDO 2 ) was recorded for each patient and the cerebral metabolic rate of oxygen (CMRO 2 ) was calculated. Clinical outcome was evaluated based on the Glasgow Outcome Scale (GOS) 6 months after rupture. Results: Following ASAH, 3 distinct hemodynamic phases arose for the entire study population. Phase I (hypoperfusion phase), occurs on the day of rupture (PHD 0) and is defined by a low ICA ED velocity (mean 17.8±1.1 cm/s), normal middle cerebral artery (MCA) velocity (mean V MCA 58.0±23.4 cm/s), and normal Lindegaard Ratio ([LR], mean 1.66±0.50). Phase II (relative hyperemia), (PHD 1–3), is characterized by an increasing ICA ED (mean 35.4±1.0 cm/s, p<0.0001), a relative hyperemia (mean CBF 15 40.1±1.5 ml/100g/minute, CMRO 2 1.17±0.41 ml/100g/min), a rising V MCA (mean 71.5±5.8 cm/sec, p<0.0001), and a rising but normal LR (mean 2.21±0.19, p<0.0001). During phase III (vasospasm phase, PHD 4–21), both the ICA ED and CBF decrease (mean ICA ED 19.9±0.9 cm/s, p<0.0001; mean CBF 15 36.8±0.7 ml/100g/minute, p=0.04), V MCA continues to rise (mean 107.6±2.9cm/sec, p<0.0001), and the LR is further increased (mean 3.25±0.08, p<0.0001). The CMRO 2 remains low (mean 1.17±0.40 ml/100g/min, p=1). Based on the GOS up to 90% of patients who experienced either a relative or absolute hyperemia had good outcomes. Conclusions: After an ASAH, 3 discrete metabolic and hemodynamic phases arise each with the potential for its own unique phase-specific management and therapy. Relative hyperemia, or “luxury perfusion,” during Phase II in the setting of non-elevated ICPs may provide some type of benefit for patients.

Intracerebral Hemorrhage after Carotid Artery Stenting without Evidence of Hyperperfusion in Positron Emission Tomography

A 75-year-old man with a recent history of transient left hemiparesis and dysarthria was referred to our hospital. Angiography showed right internal carotid artery (ICA) occlusion and left ICA 89% stenosis. Positron emission tomography (PET) showed decreased cerebral blood flow (CBF), and increased oxygen extraction fraction (OEF) and cerebral blood volume (CBV) in the right hemisphere. In the left hemisphere, CBV was increased, but CBF and OEF remained normal. One month after the transient ischemic attack, left carotid artery stenting (CAS) was performed without complications. Diffusion-weighted magnetic resonance imaging (MRI) on the day after CAS showed no fresh ischemic lesion. PET on the second day after CAS showed increased CBF and decreased OEF and CBV in the right hemisphere as compared with those before CAS. In the left hemisphere, decreased CBV was observed and CBF was slightly increased as compared with those before CAS. The postoperative course was uneventful, but on the fifth day after CAS, the patient suddenly showed a focal seizure and right motor weakness. Emergency computed tomography scanning showed massive intracranial hemorrhage with severe brain edema in the left hemisphere. Although CBF study is useful to predict the hyperperfusion syndrome, we cannot disregard the possibility of intracerebral hemorrhage after CAS for carotid artery stenosis when there is no evidence of hyperperfusion on postoperative CBF study.

A PET study of regional cerebral blood flow after experimental cardiopulmonary resuscitation

Cerebral blood flow (CBF) during cardiopulmonary resuscitation and after restoration of spontaneous circulation (ROSC) from cardiac arrest has previously been measured with the microspheres and laser Doppler techniques. We used positron emission tomography (PET) with [15O]--water to map the haemodynamic changes after ROSC in nine young pigs. After the baseline PET recording, ventricular fibrillation of 5 min duration was induced, followed by closed-chest cardiopulmonary resuscitation (CPR) in conjunction with IV administration of three bolus doses of adrenaline (epinephrine). After CPR, external defibrillatory shocks were applied to achieve ROSC. CBF was measured at intervals during 4h after ROSC. Relative to the mean global CBF at baseline (32+/-5 ml hg(-1)min(-1)), there was a substantial global increase in CBF at 10 min, especially in the diencephalon. This was followed by an interval of cortical hypoperfusion and a subsequent gradual return to baseline values.

Introduction

Introduction

How to get 133Xe into solution for blood flow studies: A technical note with an emphasis on neurosurgical patients

133Xe has been widely used for measuring blood flow in various organs. Because an injectable solution of 133Xe is not commercially available, a technique is presented that allows both the production of the radiopharmaceutical and the drawing of individualized patient doses. A system was designed to crush ampoules of 133Xe gas inside a sealed cylinder containing sodium chloride injection 0.9%. 133Xe ampoules of different sizes and filled with different activities were crushed within the system. The steel cylinder shielded 98% of the radiation. With 34 GBq 133Xe a total of 20 studies of cerebral blood flow were performed. No bacteriological contamination of the drawn doses was detected. The crusher system allows the efficient and safe production of an injectable solution of 133Xe with sodium chloride 0.9%.

Resting State Cortical Connectivity Reflected in EEG Coherence in Individuals With Autism

Theoretical conceptions of autism spectrum disorder (ASD) and experimental studies of cerebral blood flow suggest abnormalities in connections among distributed neural systems in ASD. Functional connectivity was assessed with electroencephalographic coherence between pairs of electrodes in a high-density electrode array in narrow frequency bands among 18 adults with ASD and 18 control adults in an eyes closed resting state. In the theta (3-6 Hz) frequency range, locally elevated coherence was evident for the ASD group, especially within left hemisphere frontal and temporal regions. In the lower alpha range (8-10 Hz), globally reduced coherence was evident for the ASD group within frontal regions and between frontal and all other scalp regions. The ASD group exhibited significantly greater relative power between 3 and 6 Hz and 13-17 Hz and significantly less relative power between 9 and 10 Hz. Robust patterns of over- and under-connectivity are apparent at distinct spatial and temporal scales in ASD subjects in the eyes closed resting state.

The correlation between motor impairment and cerebral blood flow in Sturge–Weber syndrome

Recent studies of regional cerebral blood flow (rCBF) and cerebral metabolism in patients with Sturge–Weber syndrome (SWS) have demonstrated a regional decrease of CBF and metabolism in the affected hemisphere, which may reflect the neurological status of the patients. Therefore, in the present study, we use stable xenon computed tomography (xenon-CT) and/or 99mtechnetium hexamethylprophylene amine oxime ( 99mTcHMPAO) single photon emission computed tomography (SPECT) to determine whether the degree of cerebral hemodynamic disturbance correlates with the severity of motor impairment in 5 children with Sturge–Weber syndrome. We found that 5 patients had great variation in clinical progression and outcome, but MR imaging investigations all revealed extensive but stable abnormalities. rCBF, assessed by stable xenon-CT and/or 99mTcHMPAO-SPECT, showed perfusion defect in all subjects. However, the xenon-CT disclosed reduction of rCBF and cerebrovascular reactivity in patients with severe motor paralysis. The total CBF and rCBF detected by xenon-CT were improved after clinical status was stabilized. We conclude that the motor function impairment in patients with SWS appeared to better correlate with the degree of rCBF impairment than with the abnormalities in conventional neuroimaging. Therefore, the quantitative CBF study is one of the diagnostic modality of choice in evaluating the neurological status in patients with SWS.

Correction for scatter and septal penetration using convolution subtraction methods and model-based compensation in 123I brain SPECT imaging—a Monte Carlo study

Scatter and septal penetration deteriorate contrast and quantitative accuracy in single photon emission computed tomography (SPECT). In this study four different correction techniques for scatter and septal penetration are evaluated for 123I brain SPECT. One of the methods is a form of model-based compensation which uses the effective source scatter estimation (ESSE) for modelling scatter, and collimator–detector response (CDR) including both geometric and penetration components. The other methods, which operate on the 2D projection images, are convolution scatter subtraction (CSS) and two versions of transmission dependent convolution subtraction (TDCS), one of them proposed by us. This method uses CSS for correction for septal penetration, with a separate kernel, and TDCS for scatter correction. The corrections are evaluated for a dopamine transporter (DAT) study and a study of the regional cerebral blood flow (rCBF), performed with 123I. The images are produced using a recently developed Monte Carlo collimator routine added to the program SIMIND which can include interactions in the collimator. The results show that the method included in the iterative reconstruction is preferable to the other methods and that the new TDCS version gives better results compared with the other 2D methods.

Consequences of Suppressing Thoughts about Tinnitus and the Effects of Cognitive Distraction on Brain Activity in Tinnitus Patients

Tinnitus is the perception of sound in the absence of any appropriate external stimulus. Based on the clinical observation that tinnitus patients may distract themselves from their sounds, we performed an experimental test on the effects of suppressing thoughts about tinnitus with 45 tinnitus patients, to systematically evaluate the immediate consequences of suppressing thought vs. attending to tinnitus. Suppression instructions tended to lead to a subsequent decrease in tinnitus-related thoughts, whereas attention to tinnitus resulted in an increase in such thoughts. No effects were seen in a control group who neither suppressed nor attended to their tinnitus. In an independent positron emission tomography study of cerebral blood flow with 8 patients we found that silent backward counting (‘serial sevens test’) led to a decrease in neural activity in auditory cortex, as well as perceived decrease of tinnitus loudness and annoyance. Thus, distraction that altered the tinnitus experience seemed to attenuate auditory cortex activity.

Less activation of the left dorsolateral prefrontal cortex in response to a meal: a feature of obesity

In an exploratory positron emission tomography study of postprandial regional cerebral blood flow, which is a marker of neuronal activity, obese men differed from lean men in several brain regions, including the prefrontal cortex. The subjects received a meal proportional to their body size; therefore, the meal volume was different for each person. We investigated whether differences in the brain responses of obese and lean men to a meal represent satiety or feelings of gastric distension. We studied 9 lean (x +/- SD body fat: 15 +/- 5%; age: 33 +/- 10 y) and 9 obese (body fat: 31 +/- 4%; age: 32 +/- 10 y) men given a fixed amount (400 mL) of a liquid meal. We compared their results with those in 11 lean (body fat: 16 +/- 5%; age: 35 +/- 8 y) and 11 obese (body fat: 33 +/- 5%; age: 28 +/- 5 y) previously studied men given a meal proportional to their body size. We performed analyses by using a two-level, random-effects approach in the STATISTICAL PARAMETRIC MAPPING software package and a significance level of P < or = 0.001, uncorrected for multiple comparisons. Compared with lean men, obese men had consistently less postprandial activation in the left dorsolateral prefrontal cortex, irrespective of meal size. Because the dorsolateral prefrontal cortex has been implicated in the inhibition of inappropriate behavior, satiety, and meal termination, differential responses of neuronal activity to food intake in this area may contribute to a propensity for obesity or to the difficulty in losing weight experienced by obese men.

P15.07: Color Doppler study of middle cerebral artery blood flow in early normal pregnancy

Transvaginal color Doppler ultrasonography was performed to analyze fetal cerebral blood flow in 62 singleton noncomplicated pregnancies. Pulsatility index in middle cerebral artery was measured. Pulsatility and peripherial flow impedance indexes decrease was observed. Sixty two pregnant women were analyzed with the transvaginal color Doppler ultrasonography. They were chosen from the group of 85 pregnant women. In 23 (27.05%) cases left, there were no signal from the middel cerebral artery observed. Women were between 10 and 16 gestation week. The avarage age of pregnant women was 26, dispersion 18–39 years old. Pulsality index level was shown and the graph for the average level in each gestation week was made. There is a characteristic linear decrease of the pulsality index level from 2.69 in 10 week to 2.09 in16 gestation week. The avarage level of pulsality index is: 2.69 in 10 week, 2.78 in 11, 2.53 in 12, 1.85 in 13, 2.13 in 14, 2.25 in 15 and 2.09 in 16 gestation week. Obtained values may be used as a reference for future investigation.

Comparison of moderate hyperventilation and mannitol for control of intracranial pressure control in patients with severe traumatic brain injury – a study of cerebral blood flow and metabolism

To compare the respective effects of established measures used for management of traumatic brain injury (TBI) patients on cerebral blood flow (CBF) and cerebral metabolic rates of oxygen (CMRO2), glucose (CMRGlc) and lactate (CMRLct). Thirty-six patients suffering from severe traumatic brain injury (TBI) were prospectively evaluated. In all patients baseline assessments were compared with that following moderate hyperventilation (reducing PaCO2 from 36 +/- 4 to 32 +/- 4 mmHg) and with that produced by administration of 0.5 gr/kg mannitol 20% intravenously. Intracranial and cerebral perfusion pressure (ICP, CPP), CBF and arterial jugular differences in oxygen, glucose and lactate contents were measured for calculation of CMRO2, CMRGlc and CMRLct. Following hyperventilation, CBF was significantly reduced (P < 0.0001). CBF remained most often above the ischemic range although values less than 30 ml x 100 gr(-1) x min(-1) were found in 27.8% of patients. CBF reduction was associated with concurrent decrease in CMRO2, anaerobic hyperglycolysis and subsequent lactate production. In contrast, mannitol resulted in significant albeit moderate improvement of cerebral perfusion. However, administration of mannitol had no ostensible effect either on oxidative or glucose metabolism and lactate balance remained mostly unaffected. Moderate hyperventilation may exacerbate pre-existing impairment of cerebral blood flow and metabolism in TBI patients and should be therefore carefully used under appropriate monitoring. Our findings rather support the use of mannitol for ICP control.

Instability of Doppler Cerebral Blood Flow in Monochorionic Twins

The purpose of this study was to evaluate Doppler flow velocity changes in cerebral vessels of monochorionic twins with twin-twin transfusion syndrome (TTTS). Repeated Doppler umbilical and cerebral blood flow studies were performed in 7 twin pairs with TTTS. Eight monochorionic twin pairs and 11 dichorionic twin pairs served as control groups. The following Doppler parameters were assessed: umbilical artery pulsatility index (PI), middle cerebral artery (MCA) PI, cerebroplacental ratio, delta PI between the umbilical artery and MCA, and peak systolic velocity (PSV) in the MCA. Significant variations in PSV in the MCA and cerebral indices were found in the study group of monochorionic twins with TTTS. Periods of high PSV with low PI in the MCA were followed by lower PSV in the same fetus. Repeated measurements in the comparison groups were stable without significant variations. The delta cerebroplacental ratio was significantly higher in the study group (0.38 versus 0.09 and 0.19 in the comparison groups; P < .02). Significant changes in Doppler flow velocity and indices suggest instability of cerebral blood flow with episodes of "hyperperfusion" in monochorionic twins with TTTS. Further studies are needed to elucidate the relationship of these transient changes to neurologic sequelae in the neonate.

Middle Cerebral Artery Occlusion Associated With Acute Myocardial Infarction in the Perioperative Period-Case Report-

A 68-year-old woman with no history of cardiac events suffered acute myocardial infarction after surgery for middle cerebral artery (MCA) occlusion manifesting as transient left motor weakness. Diffusion-weighted magnetic resonance imaging revealed multiple infarctions in the right cerebral hemisphere. Magnetic resonance angiography and cerebral angiography demonstrated an occlusion at the horizontal segment of the right MCA and no collateral circulation. Cerebral blood flow study 6 weeks after the initial presentation indicated decreased blood flow in the right cerebral hemisphere. Superficial temporal artery-MCA anastomosis was conducted to prevent recurrent cerebral infarction. Two hours after surgery, her systolic blood pressure fell to 60 mmHg and her consciousness worsened. Emergency coronary angiography indicated occlusion of the right coronary artery. Percutaneous coronary intervention was successfully performed and the subsequent course was uneventful. Preoperative evaluation of the coronary artery may be necessary before surgery for cerebral ischemic disease in both the intracranial and extracranial arteries.

Potential applications of laser polarised xenon for CBF measurements by NMR

Laser polarised (hyperpolarised) 129Xe offers a new potential way for assessment of cerebral blood flow (CBF) by nuclear magnetic resonance (NMR). We present the basic physical principles underlying noble gases'laser polarisation. Distinguishing characteristics of 129Xe NMR properties as well as theoretical basis for CBF measurement using laser polarised 129Xe are emphasized. Recent results are briefly presented and potential applications as well as current limitations of 129Xe in CBF studies are discussed.

H 2 15 O or 13 NH 3 PET and electromagnetic tomography (LORETA) during partial status epilepticus

The authors evaluated the feasibility and source localization utility of H2(15)O or 13NH3 PET and low-resolution electromagnetic tomography (LORETA) in three patients with partial status epilepticus (SE). Results were correlated with findings from intraoperative electrocorticographic recordings and surgical outcomes. PET studies of cerebral blood flow and noninvasive source modeling with LORETA using statistical nonparametric mapping provided useful information for localizing the ictal activity in patients with partial SE.

Blood Flow Imaging of the Brain: 50 Years Experience

Blood Flow Imaging of the Brain: 50 Years Experience