Non-invasive quantitative monitoring of cerebral blood flow in aneurysmal subarachnoid haemorrhage with 99mTc-ECD.

The purpose of this prospective study was to detect symptomatic cerebral vasospasm in aneurysmal subarachnoid haemorrhage (SAH) by a non-invasive mean cerebral blood flow (mCBF) quantification using 99mTc-ethyl cysteinate dimer. Measurement of mCBF without blood sampling and single photon emission tomography (SPECT) were performed at 1 and 7 days after surgery in 35 consecutive SAH patients, of whom 16 were examined at day 30 as well. A decrease in mCBF of more than 10% on day 7 versus day 1 was considered to indicate vasospasm. On visual interpretation of SPECT, a perfusion decrease which appeared newly on day 7 was considered to indicate vasospasm. In total, nine of 35 patients had cerebral vasospasm confirmed by computed tomography (CT) and/or angiography. The mCBF measurement showed a 77.8% (7/9) sensitivity, a 88.5% (23/26) specificity, a 70.0% (7/10) positive predictive value, and a 92.0% (23/25) negative predictive value. SPECT yielded a 33.3% (3/9) sensitivity, a 73.1% (19/26) specificity, a 30.0% (3/10) positive predictive value, and a 76.0% (19/25) negative predictive value. On SPECT, decreased perfusion was observed in most of the patients at clipping sites, which might represent post-operative transient abnormal perfusion and should not be read as vasospasm. In conclusion, this mCBF measurement is more accurate than visual interpretation of SPECT for detecting vasospasm.     

Noninvasive quantification of cerebral blood flow using 99mTc-ECD and SPECT.

The aim of this study was to develop a simple, noninvasive method for quantifying regional cerebral blood flow (rCBF) using 99mTc-ethyl cysteinate dimer (ECD) by a single SPECT scan and single venous sampling. METHODS: Using a three-compartment model, we introduced the regional brain fractionation index (BFI), Cb(Ts)/integral of 0-Ts Ca(tau)dtau [Ca(t), arterial input; Cb(t), brain activity]. Regional BFI obtained at the optimum time Ts (min) was converted to rCBF using an exponential function, which was obtained by analyzing the relationship between regional BFI and rCBF (= F) obtained by the standard 133Xe inhalation SPECT method. The integral of the concentration of 99mTc-ECD in arterial blood corrected for physical decay [Ca(t)] in BFI was estimated from a single venous blood sample obtained at the optimum time Tv using the regression line obtained by analyzing the relationship between the integral of Ca(t) and venous sample data. The data come from three groups of patients. The first group of patients (n = 16) underwent a complete 99mTc-ECD BFI study with measurement of Ca(t) and dynamic SPECT scanning, as well as a 133Xe inhalation study to measure rCBF The results were used to analyze the relationship between regional BFI and rCBF (obtained with 133Xe) and to determine the optimum time Ts for obtaining BFI. Data from the second group of patients (n = 15) were used to analyze the relationship between the integral of Ca(t) and venous sample data and to determine the optimum time Tv for one-point venous blood sampling. Finally, the third group of patients (8 patients, 10 studies) was used to validate the current method by comparing the results with 133Xe inhalation SPECT. RESULTS: Regional BFI obtained at time Ts = 20 min showed good agreement (r = 0.907; a = 0.552, b = 0.962) with rCBF. The venous sample data obtained at time Tv = 6 min showed a good correlation (r = 0.988) with BFI. In comparing rCBF values thus obtained and those obtained by the 133Xe method, we found a good correlation (r = 0.917, slope = 1.01). CONCLUSION: The proposed method has three advantages: (a) accurate quantification of rCBF without underestimation in the high flow range, (b) simplicity and noninvasiveness and (c) the ability to use any type of SPECT camera for the study.     

A study of the acute effect of smoking on cerebral blood flow using 99mTc-ECD SPET

Cigarette smoking is known to be associated with atherosclerosis, is an important risk factor for stroke and has other serious effects. The aim of this study was to evaluate the acute effect of cigarette smoking on cerebral blood flow using statistical parametric mapping (SPM). Ten healthy volunteers with a smoking habit were studied using technetium-99m-labelled ethylcysteinate dimer single-photon emission tomography (SPET). We evaluated the regional cerebral blood flow under the smoking and resting states. The regional cerebral blood flow on smoking-activated SPET was significantly decreased in the whole brain as compared with that on resting SPET. Our findings therefore suggest that one of the acute effects of cigarette smoking is to induce a diffuse decrease in cerebral blood flow.     

Development of an automatic analytical tool for quantitative cerebral blood flow measurement using 99mTc-ECD, and verification of clinical examples

The following process conventionally has been followed to develop quantitative images of cerebral blood flow: (1) mean cerebral blood flow (mCBF) is calculated by the Patlak plot method; (2) a SPECT slice that includes the basal ganglia is selected; and (3) based on the value of mCBF calculated by the Patlak plot method, the SPECT slice is corrected by the Lassen method and developed into a SPECT image of quantitative regional cerebral blood flow. However, this process is complicated, and the values of rCBF have been reported to fluctuate because selection of the SPECT slice and the ROI setting are in the hands of the operator. We have developed new software that automates this analysis. This software enables automatic processing simply by inputting the value of mCBF in the normal hemisphere. Since there is no need for manual operations such as setting the ROI, reproducibility is improved as well. Regional cerebral blood flow as determined by this software is quite similar to that calculated by the conventional method, so the existing clinical evaluation does not need to be changed. This software is considered to be useful.     

Improvement of the 99mTc-ECD brain uptake ratio (BUR) method for measurement of cerebral blood flow

Objective

The brain uptake ratio (BUR) method for the ^99mTc-ECD SPECT, a non-invasive measurement method of rCBF, has been used in clinical practice in Japan, because it is simple to use. However, the accuracy of this method is limited, as it has problems in the determination of input function and the regression equation. The purpose of this study is to improve the BUR method by reconstructing the determination process of the input function and regression equation based on measurement of the rCBF by H ₂ ¹⁵ O PET.

Method

The input function was obtained by setting the region of interest on the ascending aorta instead of the aortic arch. The 3DSRT algorithm was used to obtain the anatomically standardized rCBF, and developed a semi-automatic analyzing software using C++ in order to stabilize the repeatability of the improved BUR (IBUR) method. The regression equation for the IBUR method was obtained by the H ₂ ¹⁵ O PET rCBFs in 15 patients with the arterial blood sampling method. All the measurements in this study were performed with the patient in the resting state.

Result

A good correlation was observed between the rCBF values measured by H ₂ ¹⁵ O PET and the regional BURs measured by the IBUR method (r?=?0.86, p?Conclusion The BUR method was improved by changing the location of the input function from the aortic arch to the ascending aorta based on arterial blood flow dynamics, and reconstructing regression equation based on the rCBF values obtained using H ₂ ¹⁵ O PET. This finding indicates the potential clinical usefulness of this method.     

Assessment of a new non-invasive cerebral blood flow determination method using the brain uptake ratio of 99mTc-ECD

We modified the method of calculating brain uptake ratio (BUR) reported previously, and devised a new non-invasive cerebral blood flow measurements for 99mTc-ECD that does not require blood sampling. This method yields BUR that is not influenced by the gamma camera type and the choice of acquisition-reconstruction conditions, when corrected by the SPECT/Planar cross calibration coefficient. A good correlation was observed between the BUR obtained by this method and the cerebral blood flow (CBF) obtained by the 123I-IMP continuous arterial blood sampling method. And based on these results, it is now possible to convert BUR to CBF. This method is applicable to small field type of gamma cameras, and it is expected to be useful as a routine test.     

Regional cerebral blood flow pattern in normal young and aged volunteers: a99mTc-HMPAO SPET study

The aim of this study was to investigate the normal pattern of regional cerebral blood flow (rCBF) distribution in normal young and aged volunteers using technetium-99m hexamethylpropylene amine oxime (^99m-Te-HMPAO) as a tracer. The region brain perfusion of young and aged subjects was compared, especially regarding rCBF differences due to age and gender, and interhemispheric rCBF asymmetries. Sixty-eight right-handed normal volunteers — 40 young (mean age 29.5±6.3 years) and 28 aged (mean age 71.2±4.3 years) — were included in the study. rCBF was estimated on the basis of a semiquantitative approach by means of a left/right index and two region/reference ratios, using the cerebellum and the whole brain activity as references. A good correlation between these two region/reference ratios was found (P<0.005 in all cerebral regions). The highest rCBF ratios corresponded to the cerebellum, followed by the occipital lobe. The remaining cortical regions (temporal, parietal, frontal and basal ganglia) showed slightly lower values. The white matter showed rCBF ratios substantially lower than the grey matter. In neither young nor aged subjects were significant rCBF differences between the genders found in any of the two region/reference indices employed. Aged subjects showed significantly lower rCBF ratios than young subjects in the left frontal lobe and in the posterior region of the left temporal lobe. In both young and aged subjects, lower perfusion was found in the left hemisphere, except for the white matter region in both age groups and the frontal lobe in the young subjects. Aged subjects presented a slightly higher interhemispheric asymmetry in the frontal lobe. However, interhemispheric asymmetry was minimal (–1.01% to 3.14%). Consequently, a symmetrical rCBF distribution can be assumed between homologous regions, independent of age.     

Improvement in accuracy of quantitative assessment of the regional cerebral blood flow with 99mTc-ECD

Mean cerebral blood flow (mCBF) in the slice including the basal ganglia (reference slice) is necessary for the quantification of regional CBF using Patlak plot and BUR methods on 99mTc-ECD cerebral perfusion SPECT. The mCBF was calculated from the mean counts of this slice. A region of interest (ROI) has been manually set on the reference slice to obtain the mean counts (manual ROI method). However, there was large variability observed in the value of rCBF in this method. We developed a 3DSRT method for improving the accuracy of the mean counts in the reference slice and evaluated the difference between the value of rCBF on manual ROI method and that on 3DSRT method in consecutive 11 patients with cerebral vascular disease. Difference in the value of mean counts of the reference slice was distributed within the 2 standard deviations (SD) with Blant-Altman analysis in 9 of 11 patients. Significant difference in the value of mean counts between two methods was observed in 2 of 11 patients. 3DSRT method is superior accuracy to the manual ROI method in the evaluation of the counts in the ROI. Lower accuracy in manual ROI method, therefore, results in the difference of the value of mean counts. 3DSRT method provides high accuracy with the various quantitative methods for the evaluation of rCBF using 99mTc-ECD.     

Simplified quantification of regional cerebral blood flow with99mTc-ECD SPECT and continuous arterial blood sampling

The goal of this study was to develop a simple method for quantification of regional cerebral blood flow (rCBF) with^99mTc-ethyl cysteinate dinier (ECD) SPECT. Following an intravenous constant infusion of ECD for one minute, serial dynamic SPECT imaging was performed for 40 minutes in 6 healthy male volunteers with intermittent arterial blood sampling. PET scan with¹⁵O-water was performed on the same day before the SPECT study for measurement of rCBF. Arterial blood data demonstrated rapid conversion of ECD to the hydrophilic metabolites, and most of the arterial input to the brain was completed within 5 minutes after the injection. Brain activity reached a peak value soon after the cessation of infusion, and was stable thereafter with very little washout. Net extraction of ECD in the brain calculated by arterial input of ECD and rCBF demonstrated a rapid decrease within a few minutes, reaching 42.7% at 5 minutes. The simulation study suggested that the arterial blood activity obtained by continuous drawing for 5 minutes and a single SPECT scan would provide a reasonable estimate of rCBF under the assumption of constant net extraction in the brain.     

Measurement of cerebral blood flow the blood sampling method using 99mTc-ECD: simultaneous scintigram scanning of arterial blood samples and the brain with a gamma camera

To measure regional cerebral blood flow (rCBF) by blood sampling using 99mTc-ECD we devised a method of measuring the radioactive concentration in arterial blood sample with a gamma camera. In this method the head and a blood sample are placed within the same visual field to record the SPECT data of both specimens simultaneously. The results of an evaluation of the counting rate performance, applying the 30 hours decaying method using 99mTc solution showed that this method is not comparable to the well-type scintillation counter and in clinical cases the active concentration in arterial blood sample remained well within the dynamic range. In addition, examination of the influence of scattered radiation from the brain by the dilution method showed that it was negligible at a distance of more than 7.5 cm between the brain and the arterial blood sample. In the present study we placed a head-shaped phantom next to the sample. The results of the examinations suggested that this method is suitable for clinical application, and because it does not require a well-type scintillation counter, it is expected to find wide application.     

Effect of resolution recovery using graph plots on regional cerebral blood flow in healthy volunteers

Purpose

We evaluated the effect of resolution recovery (RR) using graph plots on regional cerebral blood flow (rCBF) in brain perfusion single-photon emission computed tomography (SPECT) images derived from healthy volunteers and patients diagnosed with probable Alzheimer’s disease.

Method

We acquired brain perfusion SPECT images with scatter correction (SC), computed tomography-based attenuation correction (CTAC), and RR from a three-dimensional brain phantom and from healthy volunteers. We then compared contrast-to-noise ratio, count density ratios, increase maps, and rCBF using statistical parametric mapping 8.

Results

Regional brain counts were significantly increased from 20–24% with SC, CTAC, and RR compared with SC and CTAC. Mean CBF in healthy volunteers was 42.5 ± 5.4 mL/100 g/min. Average rCBF determined using SC, CTAC and RR increased 7.5, 2.0, and 3.7% at the thalamus, posterior cingulate, and whole brain, respectively, compared with SC and CTAC.

Conclusion

Resolution recovery caused variations in normal rCBF because counts increased in cerebral regions.

     

Age-specific cerebral perfusion in 4- to 15-year-old children: a high-resolution brain SPET study using 99mTc-ECD

This study addresses the question of whether the normal range for distribution of local cerebral blood flow (lCBF) in adults can be transferred to the 4- to 15-year-old age group. Twenty-three children (age: 4–15 years; mean 11±3 years, group I) and 10 adults (age: 27–56 years; mean 45±10 years, group II) without evidence of cerebrovascular disease or other brain diseases underwent technetium-99m ethyl cysteinate dimer single-photon emission tomography. Counts in cortical and subcortical regions of interest (ROIs) were related to those in cerebellar ROIs (= 100%). Relative cortical activity in group I exceeded that in group II, particularly in left parietal (107.6%±9.8% vs 84.1%±12.4%), left frontal (97.7%±6.7% vs 79.4%±8.9%) and left temporal areas (99.7%±7.4% vs 84.9%±10.1%) and in the cingulate cortex (112.1%±9.1% vs 95.9%±10.1%, P<0.05). Cerebral activity uptake per injected dose was inversely correlated with age in 19 children of group I (r = –0.77, P<0.001). In group I, there was also an inverse correlation between age and the relative local count density in the parietal (r = –0.42 to –0.57), frontal (r = –0.48), temporal (r = –0.42 to –0.58) and occipital cortex (r = –0.44). In these cortical regions relative counts differed when subgroups of children aged 4–10 and 11–15 years were analysed. It is concluded that there are systematic differences between 4- to 15-year-old children and adults with regard to normal lCBF. Diagnostic use of perfusion agents has to consider age-adjusted normal flow maps; normal ranges should be determined separately for the age groups 4–10 and 11–15 years. Received 23 March and in revised form 11 July 1997     

Differential diagnosis in dementia using the cerebral blood flow agent 99mTc HM-PAO: a SPECT study

One of the potential clinical uses of the new cerebral blood flow agent 99mTc-hexamethylpropyleneamineoxime (HM-PAO) is the investigation of dementia, in particular to differentiate between dementia of the Alzheimer type (DAT) and multiinfarct dementia (MID). In this study 27 patients, 17 with DAT and 10 with MID, and three normal volunteers were imaged both with single photon emission CT and magnetic resonance. The HM-PAO perfusion deficits were much more common in the DAT group than in the MID group, especially in the temporoparietooccipital (TPO) regions. The two groups of patients were found to be significantly different (p less than 0.02), as regards the frequency of occurrence of bilateral TPO perfusion deficits. Four of the 17 DAT patients did not have bilateral TPO deficits but these included the three least impaired patients as assessed by psychometric testing.     

Gender difference in brain perfusion 99mTc-ECD SPECT in aged healthy volunteers after correction for partial volume effects

BACKGROUND: Previous reports have yielded controversial results concerning gender differences in regional cerebral blood flow (rCBF). To elucidate this issue, we compared 99mTc ethyl cysteinate dimer single photon emission computed tomography (SPECT) images for brain perfusion between aged-matched healthy men and women after correction for partial volume effects (PVEs). METHODS: Brain perfusion SPECT in the resting state was performed on 40 healthy, right-handed subjects, 20 men and 20 women, with an age range of 58-86 years, who did not differ sociodemographically. PVE correction was performed using grey matter volume measured by magnetic resonance imaging. Statistical parametric mapping was used for the analysis of the adjusted rCBF images of relative flow distribution. RESULTS: The PVE correction revealed that women had higher rCBF in left inferior frontal gyrus, bilateral middle temporal gyri, and left superior temporal gyrus. Men had higher rCBF in left superior frontal gyrus, right medial frontal gyrus, right superior parietal lobule, right postcentral gyrus, right cerebellum, right middle frontal gyrus, right fusiform gyrus, and right precuneus. CONCLUSION: Significant gender differences in rCBF existed in these healthy volunteers. The PVE correction of SPECT images revealed gender differences that were consistent with the universal findings of better performance on verbal tasks in women and on visuospatial tasks in men.     

Regional cerebral blood flow response to oral amphetamine challenge in healthy volunteers.

Functional brain imaging is a powerful tool for examining the central nervous system (CNS) response to pharmacologic challenges. Amphetamine is of interest both because of its role as a stimulant of the dopaminergic system and because of its use to alter mood in mood-disordered patients, particularly in patients suffering from depression. In this study, we report the effects of oral D-amphetamine relative to placebo on regional cerebral blood flow (rCBF) measured by SPECT in healthy volunteers to characterize the normal CNS response to this primarily dopaminergic stimulant. METHODS: SPECT was used to assess changes in rCBF induced by amphetamine in 16 healthy volunteers. Subjects received placebo and then 0.4 mg/kg oral amphetamine in a fixed-order single-blind design and were imaged on a triple-head tomograph. Another six healthy volunteers received placebo at both times to assess normal rCBF variability. rCBF changes were assessed with a three-dimensional voxel-based analysis integrated into an automated coregistration system. Data were automatically normalized to whole-brain counts and coregistered. Resultant rCBF changes were evaluated parametrically through the formation of an image whose voxel values were based on the paired t statistic. RESULTS: Amphetamine increased rCBF in two mesial prefrontal zones (Brodmann's areas 8 and 10), inferior orbital frontal lobe (area 11), brain stem (ventral tegmentum), anteromesial temporal lobe (amygdala), and anterior thalamus. Amphetamine decreased rCBF to motor cortex, visual cortex, fusiform gyrus, posterolateral temporal lobe, and right lateral temporal lobe. CONCLUSION: Our data suggest that amphetamine induces focal increases and decreases in rCBF in healthy volunteers in areas primarily innervated by dopamine pathways and in areas with secondary (primarily limbic) affiliations. These data are consistent with glucose metabolic data from autoradiographic studies in animals, in which the largest increases are seen in brain stem, followed by striatum, thalamus, and frontal and sensory cortices. Frontopolar and temporal increases observed in our study appear to be unique to humans.     

Regional cerebral blood flow measurement using a scintillation camera.

A scintillation camera connected to auxillary equipment with off-line data processing or connected to an on-line dedicated computer system permits measurement of hemispheric and regional cerebral blood flow. Reliable flow values are obtained from regions limited in size by spatial resolution and the count rates achieved. Flow measurements obtained with the camera are able to resolve inhomogeneities of cerebral circulation in normal subjects. In a variety of clinical conditions, the localization, severity and extent of flow alterations are shown. Results of flow measurements in individual cases elucidate the pathogenesis of neurologic deficits, quantify the damage to the brain, indicate therapeutic measures of potential value and permit an estimation of the further clinical course. With restricted spatial resolution, flow measurements after intravenous 133Xe injection are also feasible.