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.     

Increased cerebral blood flow in MELAS shown by Tc-99m HMPAO brain SPECT

We report cerebral SPECT studies on two siblings with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Tc-99m HMPAO brain SPECT was performed 8, 19 and 30 days after a stroke-like episode in one case and 10 days after a stroke-like episode, 6 h after a partial seizure and as a follow-up study in the other. Increased blood flow was seen in both these patients with stroke-like episodes due to MELAS. The cause of the increased blood flow is uncertain, but it may be related to the decreased pH created by local increase in lactic acid. Received: 30 December 1997/Accepted: 18 March 1999     

Regional cerebral blood flow changes in chronic alcoholism using Tc-99m HMPAO SPECT. Comparison with CT parameters.

Twenty-eight patients were studied for regional cerebral blood flow changes as a result of chronic alcoholism. After the administration of 550 to 600 MBq Tc-99m HMPAO, tomographic slices were obtained using a SPECT camera. Eight regions per hemisphere were drawn on each transaxial section, and tracer redistribution was calculated for each region. Region-to-whole slice ratios were determined for each patient. Patients had significantly decreased frontal/whole slice (1 +/- 0.02) ratios in comparison with a normal group (p less than 0.01). Twenty-four out of 26 patients (85.7%) demonstrated abnormal rCBF. Eighteen out of 28 (64.3%) showed activity lower in the left hemisphere than in the right. Using CT parameters, 60% of the patients had either sulcal widening and/or ventricular enlargement. The frontal region and the left hemisphere were more affected by alcohol than other regions. More cerebral blood flow changes than morphologic changes were found caused by alcoholism.     

Tc-99m HMPAO/SPECT determination of regional cerebral blood flow changes in schizophrenics

Hypofrontality (hypometabolism and hypoperfusion) has been demonstrated in patients with schizophrenia by the use of several imaging methods, such as positron emission tomography (PET). In this study, Tc-99m hexamethylpropylene amineoxime (HMPAO) and SPECT were used to investigate regional blood flow changes in 20 schizophrenic patients (12 males and 8 females, aged 15-50 years) experiencing acoustic hallucinations. Tc-99m HM-PAO (15-20 mCi) was injected intravenously, eight regions/hemisphere were drawn on transaxial sections, and tracer redistribution was calculated for each region. Frontal/occipital ratios (0.917 +/- 0.045) and frontal/whole-slice ratios (0.984 +/- 0.036) were determined for each patient. The patients had significantly lower frontal/occipital ratios (P less than 0.0005) and lower frontal/whole-slice ratios (P less than 0.01) in comparison to a normal group (11 cases).     

MR relative cerebral blood flow mapping of Alzheimer disease: correlation with Tc-99m HMPAO SPECT

RATIONALE AND OBJECTIVES: To evaluate the value of magnetic resonance (MR) perfusion imaging for diagnosis of Alzheimer disease (AD), the authors compared relative cerebral blood flow (CBF) maps obtained with MR perfusion imaging and technetium-99m hexamethyl-propyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) in patients with AD. MATERIALS AND METHODS: Eight patients with AD were studied with MR perfusion imaging and HMPAO SPECT. The relative CBF maps from the two techniques were spatially coregistered, and relative CBF values in 13 cerebral gray matter regions (total, 26 regions of interest) were compared with regression analysis. To evaluate the degree of deviation of each brain region from the regression line, a P value for the residual was calculated for each region. RESULTS: A significant overall correlation was seen between the relative CBF values produced by the two techniques (r = .68, P < .0001). Smaller P values for the residuals were obtained in the anterior cingulate cortex (P = .05) and posterior cingulate cortex (P < .001), indicating larger deviations in these regions. When data from these two regions were eliminated, the correlation coefficient rose to 0.80 (P < .0001). CONCLUSION: Despite fairly large discrepancies in the anterior and posterior cingulate cortices, the relative CBF map obtained with MR imaging is generally in close agreement with the HMPAO SPECT map, suggesting that MR perfusion imaging can provide clinically useful information regarding CBF abnormalities in patients with AD.     

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.     

Noninvasive measurements of regional cerebral blood flow using technetium-99m hexamethylprophylene amine oxime

The previously reported method for quantitative measurements of whole-brain or hemispheric-brain perfusion using technetium-99m hexamethylpropylene amine oxime (HMPAO) radionuclide angiography is now further developed so that regional cerebral blood flow (rCBF) can be measured. Lassen's correction algorithm is used for the linearization of a curve-linear relationship between the radioactivity in the brain and blood flow as seen with single-photon emission tomography (SPET) images. In this algorithm, the cerebral hemisphere was chosen as the reference region and the correction factor was adapted to rCBF in the reference region. This new method of measuring CBF from SPET has been validated in 33 normal subjects and 22 patients with cerebrovascular disease. Regional CBF values in 20 brain regions of the normal subjects were in good agreement with reported values measured by other methods. Regional CBF in the frontal cortex was greater than that in the temporal, parietal or occipital cortex for the entire age range. This hyperfrontal perfusion tended to be less pronounced with advancing age. Seventeen patients with unilateral brain infarction showed significantly lower rCBF than normal subjects. The infarct core showed a low rCBF value of 11.1 ml/ 100 g/min on average. An increase in rCBF after acetazolamide administration was observed and mesured with this method in five patients with unilateral occlusive vascular pathology. These results suggest that this non-invasive method (without any blood sampling) permits the routine measurement of rCBF from HMPAO SPET tomograms of blood flow. Correspondence to: H. Matsuda     

Quantification of regional cerebral blood flow (rCBF) using 99Tcm-HMPAO and SPECT: choice of the reference region.

The effects of the choice of the reference region in determining the relative regional cerebral blood flow (rCBF) using 99Tcm-hexamethylpropylene amine oxime (HMPAO) single photon emission tomography (SPECT) have been studied in order to establish or exclude it as a cause of inconsistencies in these studies. Relative rCBF was estimated by normalizing the regional count densities to two reference regions, the cerebellum and the whole slice, in 35 patients with Alzheimer's disease (AD), 25 patients with chronic schizophrenia (SCH) and the same number of matched normal volunteers. The statistical significance of the differences in rCBF between patients and their matched normals varied in the two sets of rCBF data. Smaller differences were highly significant while some larger differences were of less significance with whole slice normalization. The results suggest that the choice of reference region is one of the causes resulting in discrepancies in the results from various centres. The need to use a standard reference region is indicated.     

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.     

Regional brain blood flow in congenital dysphasia: studies with technetium-99m HM-PAO SPECT

Congenital dysphasia is a developmental speech disorder not explained by deafness, phonation disorder, mental retardation, neurologic lesion, or psychiatric disease. The existence of brain lesions has often been postulated but conventional investigations fail to demonstrate any cerebral abnormality. By means of [99mTc]hexamethyl-propyleneamine oxime (HM-PAO) brain single photon emission computed tomography (SPECT) we have studied 14 children suffering from congenital dysphasia. The brain computed tomographic scan was normal in all cases. In two patients with expression impairment the SPECT study demonstrated a hypoperfusion in the inferior frontal convolution of the left hemisphere, involving the Broca's area. In nine of 12 patients with global dysphasia (deficits in both comprehension and expression), SPECT study showed two hypoperfused areas: an abnormality in the left temporoparietal region and a hypoactivity in the upper and middle areas of the right frontal lobe. These results suggest that congenital dysphasia could be due, like acquired aphasia, to specific impairment of the language cerebral areas and that brain SPECT studies with [99mTc]HM-PAO could be useful for a better comprehension of the physiopathology of these disorders.     

The study of regional cerebral blood flow in stroke patients using technetium 99m HMPAO

Seventeen patients who had suffered a stroke in the previous 72 h have been studied using technetium 99m hexamethyl propylene amine oxime (HMPAO) to assess cerebral blood flow. Comparison of the scan appearances and clinical signs were made in all cases. Twelve of the patients had a repeat HMPAO scan 14 days later, together with further clinical assessment. Good correlation between the size and site of perfusion deficit and the clinical signs was found in 14 of the patients. When the results of the 12 patients who had repeat scans were examined at 14 days the correlation between the scan and the clinical signs was less accurate and it seems unlikely that the assessment of the size of cerebral infarction as demonstrated by an HMPAO scan will provide an accurate prognostic sign. Three of the patients, all of whom had suffered right hemiplegia and were dysphasic, had regions of increased uptake adjacent to the area of ischaemia and non deteriorated clinically; it is thought that this sign may represent hyperperfusion around infarction and indicates a fair prognosis. In patients suffering from transient neurological symptoms, the use of HMPAO may be useful by excluding the presence of other cerebral disease.     

Comparative study of regional cerebral blood flow images by SPECT using xenon-133, iodine-123 IMP, and technetium-99m HM-PAO

Regional cerebral blood flow (rCBF) was measured by single photon emission computed tomography (SPECT) using 133Xe, N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP) and [99mTc] hexamethylpropyleneamine oxime ([99mTc]HM-PAO) in 24 patients with cerebrovascular diseases. The greatest advantage of 133Xe SPECT was to be able to provide absolute rCBF values without arterial sampling. However, its image quality was very poor. Iodine-123 IMP SPECT provided rCBF images of higher quality and it had good correlation to 133Xe SPECT. Iodine-123 IMP SPECT provided the best images to detect mild ischemic lesions. It could detect obstructive or stenotic changes of large cerebral arteries very well except for a moderate stenosis of internal carotid artery. Technetium-99m HM-PAO SPECT also provided very good rCBF images and it had good correlation to 133Xe SPECT. However, the count-density ratios for the ischemic lesions to the contralateral presumed normal areas of [99mTc] HM-PAO SPECT were significantly higher than those of [123I]IMP SPECT.     

A study of acetazolamide-induced changes in cerebral blood flow using99mTc HMPAO SPECT in patients with cerebrovascular disease

For semiquantification of SPECT studies we tried to calculate cerebral^99mTc-HMPAO uptake related to injected dose and estimated brain volume. The method was applied to SPECT investigations of 27 patients who had a least one ischaemic attack and a confirmed 80–100% stenosis of the corresponding internal carotid artery (ICA). Vascular reactivity was tested by parenteral administration of acetazolamide (AZ). Increase in HMPAO uptake after AZ was evident in both hemispheres, although the increase (AZ effect) was significantly lower in the affected hemisphere (+24% versus +28%). No interhemispheric uptake differences were seen in patients with largely normal SPECT studies, although local asymmetries in HMPAO deposition were visible. Patients with low density lesions on CT and with a well-demarcated lesion in the same location on SPECT revealed interhemispheric uptake differences, with lower uptake on the affected side. This was not due solely to alterations in the lesion, but also to reduced HMPAO uptake and AZ effect in the surrounding area. The AZ effect showed no correlation with angiographic findings, indicating no major haemodynamic influence of the ICA stenosis on cerebral hemisphere perfusion. Calculated cerebral HMPAO uptake changes after AZ administration were in good accordance with absolute cerebral blood flow measurements, and made interindividual comparisons possible. However, as changes in the area around an infarct or local reduction in vascular reserve may not be reproduced adequately by uptake calculations, visual inspection is still necessary.     

儿童病毒性脑炎~(99)Tc~m-ECD SPECT脑血流显像的研究

目的　探讨99Tcm 双半胱乙酯 (ECD)SPECT脑血流显像在儿童病毒性脑炎中的显像特点和应用价值。方法　对 2 2例临床诊断为病毒性脑炎患儿进行99Tcm ECDSPECT脑血流显像 ,4例于治疗后 13～ 40d进行复查。结果　病毒性脑炎急性期 2 2例患儿中 2 1例脑SPECT显示异常。 17例为多发病灶 ,其中可有双侧对称性或不对称性改变 ;4例为单发病灶。病变处可表现为血流高灌注、低灌注或两者并存。治疗后高灌注区可转变为正常灌注或低灌注 ,低灌注区可转变为正常灌注或持续存在 ;转变为正常灌注者预后可能好于转变为低灌注者。结论　①儿童脑血流显像异常的判断需依据正常同龄儿童的脑显像特点。②99Tcm ECDSPECT脑血流显像可作为病毒性脑炎辅助诊断、预后监测的有效手段     

Quantification of regional cerebral blood flow using 99mTc-HMPAO SPECT and intravenous 133Xe injection method]

We converted an absolute value of 133Xe-CBF (initial slope index, ISI) to the three dimensional CBF-SPECT using the intravenous 133Xe injection technique and 99mTc-HMPAO SPECT according to the microsphere model (method A), and the three compartment model described by Lassen et al. (method B): [formula: see text] [formula: see text] where f = flow in the region of interest (ROI), fr = flow in the reference region, C = count density of 99mTc-HMPAO SPECT in the ROI, Cr = count density of 99mTc-HMPAO SPECT in the reference region, and alpha = conversion to clearance ratio of HMPAO. We used alpha value of 1.5, and the whole cerebrum as a reference region. Four asymptomatic subjects and 15 patients with ischemic cerebrovascular disease were entered the study. In method A, excellent correlation was seen between ISI and SPECT-CBF in both of the cerebral hemisphere (r = 0.993; p < 0.001, n = 38) and the cerebellar hemisphere (r = 0.901; p < 0.001, n = 38). When back diffusion of HMPAO was corrected by method B, correlation coefficient of SPECT-CBF with ISI was equivalent to that in method A in the cerebrum (r = 0.978; p < 0.001, n = 38), while the correlation coefficient ih the cerebellum was lowered (r = 0.726; p < 0.001, n = 38) although high flow to low flow ratio was increased. Reproducibility of rCBF assessed 1 week apart from the first CBF-SPECT was highly reproducible in all of the brain regions; correlation coefficient ranged from 0.757 to 0.910 with a mean correlation coefficient of 0.834 (n = 11). The slope and intercept of the linear regression line between 2nd rCBF versus 1st CBF were 0.889 (range, 0.791-1.141) and 5.5 (range, -9.1-13.4), respectively. Regional CBF measured by method B was approximately 20% increase from that measured by method A. However, there was no significant difference in the reproducibility of rCBF between the two methods. Our results indicate that rCBF can be simply and noninvasively quantified using 99mTc-HMPAO SPECT and absolute unit of CBF measured by 133Xe injection technique. SPECT-CBF offers high resolution images and may be applicable for various cerebrovascular disorders in routine clinical use.     

Quantification of cerebral blood flow using technetium-99m ethyl cysteinate dimer and single-photon emission tomography

The aim of this study was to develop a new method for quantifying regional cerebral blood flow (rCBF) with technetium-99m ethyl cysteinate dimer (ECD) and single-photon emission tomography (SPET). Employing a three-compartment model, we introduced a parameter, regional brain fractionation index (BFI), that reflects rCBF values and is obtained by a single SPET scan at optimum time T (min) after tracer injection and the integral of arterial input. By analysing the dynamic SPET and arterial blood sampling data of 15 subjects, including the results of acetazolamide challenges, with the graphical plot method, optimum time T was determined to be approximately 20 min post injection. Regional BFI values of each subject were calculated from the single SPET data at 20 min and arterial input. The relationship between the values of regional BFI and rCBF obtained by xenon-133 inhalation SPET was analysed by approximation with an exponential function, resulting in good agreement (r = 0.907). In the present method, rCBF values were determined from regional BFI values by using the inverse exponential function as a non-linear regression curve. To validate the method, we applied it to six other subjects, in whom acetazolamide challenges were also performed. In comparing rCBF values thus obtained and those obtained by ¹³³Xe inhalation SPET, we found a good correlation (r = 0.901) with an inclination approximating 1 (= 1.02) and without underestimation of rCBF in the high-flow range. Since the present method does not require dynamic planar imaging or dynamic SPET scanning, it can be applied to any type of SPET scanner and is useful in clinical SPET studies. Received 1 August 1998 and in revised form 28 October 1998     

Quantification of cerebral blood flow using technetium-99m ethyl cysteinate dimer and single-photon emission tomography

The aim of this study was to develop a new method for quantifying regional cerebral blood flow (rCBF) with technetium-99m ethyl cysteinate dimer (ECD) and single-photon emission tomography (SPET). Employing a three-compartment model, we introduced a parameter, regional brain fractionation index (BFI), that reflects rCBF values and is obtained by a single SPET scan at optimum time T (min) after tracer injection and the integral of arterial input. By analysing the dynamic SPET and arterial blood sampling data of 15 subjects, including the results of acetazolamide challenges, with the graphical plot method, optimum time T was determined to be approximately 20 min post injection. Regional BFI values of each subject were calculated from the single SPET data at 20 min and arterial input. The relationship between the values of regional BFI and rCBF obtained by xenon-133 inhalation SPET was analysed by approximation with an exponential function, resulting in good agreement (r = 0.907). In the present method, rCBF values were determined from regional BFI values by using the inverse exponential function as a non-linear regression curve. To validate the method, we applied it to six other subjects, in whom acetazolamide challenges were also performed. In comparing rCBF values thus obtained and those obtained by 133Xe inhalation SPET, we found a good correlation (r = 0.901) with an inclination approximating 1 (= 1.02) and without underestimation of rCBF in the high-flow range. Since the present method does not require dynamic planar imaging or dynamic SPET scanning, it can be applied to any type of SPET scanner and is useful in clinical SPET studies.