Xenon CT cerebral blood flow in patients with head injury: influence of pulmonary trauma on the input function

The noninvasive xenon-enhanced CT (Xe CT) cerebral blood flow (CBF) method has been used in patients with severe traumatic brain injury (TBI) to identify the blood-flow thresholds for the development of irreversible ischaemia or infarction following severe TBI. Quantitative regional CBF (rCBF) estimates are based on the assumption of identity between the end-tidal xenon concentration curve, used as the input function, and the arterial xenon concentration curve, being the true input function to the brain. Accordingly, rCBF data addressing the issue of ischaemia should be viewed in relation to possible deviations between the end-tidal and arterial xenon concentration curves. To evaluate this possible source of error, we studied five patients with severe TBI (Glasgow coma score ≤ 7) who also had pulmonary trauma. CBF was studied with the Xe CT CBF method and flow rates were determined by fitting the Kety equation to each CT voxel using either the end-tidal or the arterial xenon curve as input function. In all patients rCBF estimates were lower using the end-tidal xenon curve than with the arterial xenon curve; the mean underestimation was 20.3 % in gray metter and 17.3 % in white matter. The deviation between the end-tidal and arterial xenon concentration curves should be considered as a source of error when defining critical flow values according to the flow thresholds of tissue viability Received: 1 June 1999/Accepted: 23 July 1999     

Correlation of regional cerebral blood flow measured by stable xenon CT and perfusion MRI

PURPOSE: The purpose of this work was to investigate the validity of perfusion MRI in comparison with stable xenon CT for evaluating regional cerebral blood flow (rCBF). METHOD: The rCBF was measured by xenon CT and perfusion MRI within a 24 h interval in 10 patients (mean +/- SD age 63 +/- 10 years). For perfusion MRI, absolute values of rCBF were calculated based on the indicator dilution theory after injection of 0.1 mmol/kg of Gd-DTPA. Eight to 10 regions of interest (37 mm2) were located in the white and gray matter on the rCBF images for each of the 10 patients. RESULTS: The mean +/- SD values of rCBF in gray matter were 48.5 +/- 14.1 ml/100 g/min measured by xenon CT and 52.2 +/- 16.4 ml/100 g/min measured by perfusion MRI. In the white matter, the rCBF was 22.6 +/- 9.1 ml/100 g/min by xenon CT and 27.4 +/- 6.8 ml/100 g/min by perfusion MRI. There was a good correlation of rCBF values between perfusion MRI and xenon CT (Pearson correlation coefficient 0.83; p < 0.0001). CONCLUSION: Comparable to xenon CT, perfusion MRI provides relatively high resolution, quantitative local rCBF information coupled to MR anatomy.     

Physiologic changes in regional cerebral blood flow defined by xenon-enhanced CT scanning

Summary With adequate concentrations of commercially available nonradioactive xenon an enhancement of brain substance was readily demonstrated by computed tomography (CT). By performing successive CT scans at a fixed brain level following xenon inhalation, the partition coefficient and clearance of xenon as well as the regional cerebral blood flow (rCBF) could be calculated. The expected physiologic alterations in rCBF with acute cerebral infarction and changes in arterial CO₂ were accurately defined by xenon-enhanced CT scanning affirming the potential future applications of this technique.     

Hemisphere cross talk and signal overlapping in bilateral regional cerebral blood flow measurements using xenon 133

In bilateral regional cerebral blood flow measurements with xenon 133, Compton scatter and hemispheric cross talk obscure the regional resolution and increase the uncertainty of the results. In order to evaluate the effects of these extraregional signal sources on the calculation of regional gray matter blood flow, a computerized simulation procedure was developed. Using the depth-response of a rCBF detector in combination with a computer model of the human brain, it was possible to calculate the signal contributions from different regions in the brain. The results obtained show that large errors may be introduced in the calculation of regional gray matter blood flow when flow assymetries exist.     

Perfusion measurements of the brain: using dynamic CT for the quantitative assessment of cerebral ischemia in acute stroke

Objective: Perfusion CT has been successfully used as a functional imaging technique for the differential diagnosis of patients with hyperacute stroke. We investigated to what extent this technique can also be used for the quantitative assessment of cerebral ischemia. Methods and material: We studied linearity, spatial resolution and noise behaviour of cerebral blood flow (CBF) determination with computer simulations and phantom measurements. Statistical ROI based analysis of CBF images of a subset of 38 patients from a controlled clinical stroke study with currently more than 75 patients was done to check the power of relative cerebral blood flow (rCBF) values to predict definite infarction and ischemic penumbra. Classification was performed using follow-up CT and MR data. Results: Absolute CBF values were systematically underestimated, the degree depended on the cardiac output of the patients. Phantom measurements and simulations indicated very good linearity allowing reliable calculation of rCBF values. Infarct and penumbra areas in 19 patients receiving standard heparin therapy had mean rCBF values of 0.19 and 0.62, respectively. The corresponding values for 19 patients receiving local intraarterial fibrinolysis were 0.18 and 0.57. The difference between infarct and penumbra values was highly significant (P<0.0001) in both groups. No penumbra area was found with an rCBF value of less than 0.20. While in the heparin group only 25% of all areas with an rCBF between 0.20 and 0.35 survived, in the fibrinolytic group 61% of these areas could be saved (P<0.05). Conclusion: Perfusion CT is a fast and practical technique for routine clinical application. It provides substantial and important additional information for the selection of the optimal treatment strategy for patients with hyperacute stroke. Relative values of cerebral blood flow discriminate very well between areas of reversible and irreversible ischemia; an rCBF value of 0.20 appears to be a definite lower limit for brain tissue to survive an ischemic injury.     

Comparison of methods of attenuation and scatter correction in brain perfusion SPECT

OBJECTIVE: The radioactivity count distribution in the brain must be determined accurately to accurately measure cerebral blood flow (CBF). Scatter and attenuation are factors that compromise the accuracy of determining radioactivity counts in the brain. METHODS: We compared regional CBF in patients by an autoradiographic method using N-isopropyl-p-[123I] iodoamphetamine when, first, attenuation correction alone was performed uniformly on SPECT images by using empiric mu-values (Chang method); second, scatter correction was performed and the mu-values of a homogeneous-attenuation body of water were used for attenuation correction (triple-energy window [TEW]+Chang method); and third, scatter correction was performed and the mu-values calculated by CT were used for attenuation correction (TEW+CT method). We also compared regional CBF measured by these methods with the values obtained by the xenon CT/CBF method, which uses CT and stable xenon. RESULTS: Scatter correction reduced overestimation of regional CBF in low-flow regions. The TEW+CT method yielded better regional and overall correlations with the xenon CT/CBF method than did either of the other methods. CONCLUSION: The TEW+CT method of correction gave the most accurate measurements of regional CBF.     

Quantitative cerebral blood flow calculation method using white matter lambda in xenon CT

The objective of this work is to propose a quantitative cerebral blood flow (CBF) calculation method for xenon CT (Xe-CT) by logically estimating the time course change rate (rate constant) of the arterial xenon concentration from that of end-tidal xenon concentration. A single factor, gamma (gamma), which is considered to reflect the diffusing capacity of the lung for xenon, was introduced to correlate the end-tidal rate constant (Kend-tidal) with the arterial rate constant (Karterial). When an appropriate value is given to gamma, it is possible to calculate the arterial rate constant (calculated Karterial) from Kend-tidal. A procedure was developed to determine the gamma value utilizing the characteristics of white matter lambda (lambda). This procedure was applied to three healthy volunteers. The gamma gammaalues for the three subjects were consistent with those directly calculated from end-tidal and arterial (abdominal aorta) xenon data. Hemispheric CBF values with use of calculated Karterial (47.3 +/- 10.3 ml/100 g/min) were close to the reported normative values. We conclude this method could make current Xe-CT examinations substantially reliable and quantitative in measuring CBF.     

Comparative studies of computed tomography and measurements of regional cerebral blood flow in stroke patients

Summary Comparative studies of computed tomography and of regional cerebral blood flow (rCBF) by means of the intracarotid xenon-133-clearance method were performed in 25 stroke patients. The relationships between an infarction in CT and disturbances of rCBF, between a normal CT in stroke cases and focal changes of CBF, and between the luxury perfusion syndrome in the rCBF study and contrast enhancement of an infarct in CT are demonstrated and discussed.     

Xenon/computed tomography cerebral blood flow measurements. Methods and accuracy

We performed a series of five baboon experiments to compare cerebral blood flow measured with an improved stable xenon/CT method and the radiolabelled microsphere technique at a PaCO2 of 40 mm Hg. The xenon/CT method was implemented by fitting the arterial xenon uptake with a double exponential function, by measuring the oxygen and carbon dioxide concentrations continuously during each breath and by taking into account the lung-to-brain transit time of xenon. The time of xenon inhalation was extended to 30 minutes to obtain more reliable estimates of CBF in white matter regions. The results indicate an overall correlation coefficient of 0.92 between the two methods and good numeric agreement.     

Input parameter sensitivity analysis and comparison of quantification models for continuous arterial spin labeling.

The regional cerebral blood flow (rCBF) values determined using continuous arterial spin labeling (CASL) are subject to several sources of variability, including natural physiologic variations, sensitivity to the input parameters, and the use of different quantification models. To date, a thorough analysis of the impact of input parameters and the choice of quantification model has not been performed. These sources of variability were investigated through computer simulations using bootstrap techniques on actual CASL data. Coefficients of variation for representative single voxels were 6.7% for gray matter and 29% for white matter, and for eight-voxel regions of interest they were 4.5% for gray matter and 23% for white matter. Comparison of nine CASL quantification models showed differences in gray matter rCBF values of up to 42%. An analysis of the sensitivity of the rCBF to input parameters for each of the nine quantification models demonstrated that accurate quantification of the inversion efficiency, tissue and arterial blood longitudinal relaxation times, and transit times were critical in calculating precise rCBF values. The large potential variations in rCBF and the effect of the choice of quantification model suggest that interpreting absolute rCBF values in CASL studies can be challenging and requires great care.     

Comparative cranial CT enhancement in the normal primate

The application of intravenous, intrathecal, and inhalation enhancement techniques to the CT evaluation of the nonhuman primate (Papio cynocephalus/anubis) is described. The falx cerebri cortical vasculature, vein of Galen, straight sinus and tentorium cerebelli were defined with intravenous enhancement. Intrathecal CT enhancement with air was limited by distortion in cerebrospinal fluid spaces. Intrathecal CT enhancement using a low dose of metrizamide accurately delineated the subarachnoid spaces and the brain substance they surrounded with minimal morbidity. Symmetrical brain enhancement (perfusion) was prominent following inhalation CT enhancement; the degree of enhancement correlated with the estimated xenon concentration in the bloodstream. In addition, by performing repeated CT scans during the clearance of xenon from the brain, an approximate analysis of regional cerebral blood flow was obtained.     

Xenon contrast-enhanced CT imaging of supratentorial hypoperfusion in patients with brain stem infarction

BACKGROUND AND PURPOSE: The characteristics of hypoperfusion in the supratentorial region of patients with brain stem infarction are unclear. We investigated the relationships between the presence of hypoperfusion and the location, number, and size of the infarcts with xenon contrast-enhanced CT. METHODS: One hundred five patients with brain stem infarction detected by MR imaging underwent xenon contrast-enhanced CT to measure the regional CBF (rCBF) in the frontal, temporal, parietal, and occipital regions and in the putamen and thalamus. A decrease of more than 10% from the mean rCBF value for normal individuals was considered to indicate hypoperfusion. RESULTS: Thirty-six patients had supratentorial hypoperfusion. The mean rCBF values (measured in mL/100 g/minute) were as follows: frontal region, 36.2 +/- 5.1 (-14.8%, n = 28); parietal region, 42.3 +/- 4.7 (-19.1%, n = 29); temporal region, 41.5 +/- 2.8 (-12.6%, n = 12); and thalamus, 50.1 +/- 3.2 (-19.6%, n = 7). Supratentorial hypoperfusion was associated with pontine infarction in 33 patients (upper pons in 15, middle pons in 18, and lower pons in seven), midbrain infarction in two, and medulla infarction in one. Twenty-three patients had infarcts that were larger than 5 mm, and 11 had infarcts that were 2 to 5 mm. Only two had infarcts that were smaller than 2 mm. Seven patients each had one infarct, 13 each had two, and 16 each had three. CONCLUSION: Supratentorial hypoperfusion was associated with larger infarcts, with more infarcts, and with pontine infarction.     

Remote effects in MCA territory ischemic infarction: a study of regional cerebral blood flow and oxygen metabolism using positron computed tomography and 15O labeled gases

Using positron computed tomography (PCT) and the 15O labeled gas steady-state inhalation technique, regional cerebral blood flow (rCBF), cerebral oxygen consumption (rCMRO2), and oxygen extraction fraction (rOEF) can be measured quantitatively in humans. We quantitatively examined the relationship between focal ischemic lesions and intact regions as detected by X-ray CT in such areas as the territory of the contralateral middle cerebral artery (MCA), thalami, pons, and cerebellar hemispheres. Twenty-three PCT measurements in 13 patients with unilateral ischemic infarction in the MCA territory as detected by X-ray CT were performed. Remote effects from cerebral infarction of the MCA territory were observed in the contralateral MCA territory, ipsilateral thalamus, brainstem, and contralateral cerebellar hemisphere. Slight depression of rCBF and rCMRO2 was also observed in the contralateral thalamus and ipsilateral cerebral hemisphere; rOEF was normal in these areas. Though the depression of rCBF and rCMRO2 due to remote effects was detected in all periods, it was mildly observed 0 to 6 days after onset. The reduction of rCBF and rCMRO2 due to remote effects was less than the morphological as well as the functional threshold. The phenomenon is probably caused by neuronal deactivation, and the regions with depressed blood flow and metabolism may be in a "resting" state.     

Measurement of cerebral hemodynamics with perfusion-weighted MR imaging: comparison with pre- and post-acetazolamide 133Xe-SPECT in occlusive carotid disease

BACKGROUND AND PURPOSE: We generated regional cerebral blood volume (rCBV) and regional cerebral blood flow (rCBF) studies from dynamic susceptibility contrast-enhanced MR images after an intravenous bolus injection of contrast agent (perfusion-weighted imaging [PWI]) by applying indicator dilution theory. We used a multishot echo-planar imaging (EPI) sequence to obtain adequate arterial input function (AIF). Our purpose was to compare the cerebral hemodynamics measured by PWI with the rCBF values and cerebral perfusion reserve obtained by xenon-133 single-photon emission CT (133Xe-SPECT). METHODS: Eight patients with chronic internal carotid artery occlusion or stenosis were examined. PWI data were acquired using a multishot EPI sequence, and the AIF was determined automatically. Our procedure was based on indicator dilution theory and deconvolution analysis. To eliminate the effect of superficial vessels, the automatic threshold selection method was used. RESULTS: AIF was adequate to generate rCBF and rCBV images. The rCBF and rCBV images by PWI were superior to 133Xe-SPECT scans in spatial resolution, and the rCBF values obtained by PWI correlated well with those obtained by 133Xe-SPECT. The regions with severely decreased perfusion reserve, which were determined by pre- and post-acetazolamide 133Xe-SPECT, showed significantly lower rCBF and higher rCBV by PWI than did regions with normal and moderately decreased perfusion reserve. CONCLUSION: The rCBF and rCBV images generated by our procedure using PWI data appear to provide important clinical information for evaluating the degree of cerebral perfusion reserve impairment in patients with chronic ischemia.     

Regional cerebral blood flow and blood volume in patients with subcortical arteriosclerotic encephalopathy (SAE)

The aim of the present study was a detailed analysis of the regional cerebral blood flow and blood volume in patients with subcortical arteriosclerotic encephalopathy (SAE) by means of functional magnetic resonance imaging (MRI). A group of 26 patients with SAE and a group of 16 age-matched healthy volunteers were examined. Using a well-established dynamic susceptibility contrast-enhanced MRI method, the regional cerebral blood flow (rCBF) and blood volume (rCBV) were quantified for each subject in 12 different regions in the brain parenchyma. As compared to healthy volunteers, patients with SAE showed significantly reduced rCBF and rCBV values in white matter regions and in the occipital cortex. Regions containing predominantly grey matter show almost normal rCBF and rCBV values. In conclusion, quantitative analysis of rCBF and rCBV values demonstrates clearly that SAE is a disease that is associated with a reduced microcirculation predominantly in white matter.     

Brain single photon emission computed tomography: newer activation and intervention studies

Single-photon emission computed tomography (SPECT) regional cerebral blood flow (rCBF) findings using non-xenon 133 tracers in combination with activation and intervention techniques are reviewed. Examination of the currently available data indicates that it is possible to detect the effects of a variety of activations and interventional procedures using SPECT rCBF with non-xenon 133 tracers. There are still many issues to be resolved before SPECT can reach the level of sophistication attained by xenon 133 and positron emission tomography in studying rCBF during activation or intervention. However, research to date indicates that SPECT rCBF studied with tracers other than xenon 133 has an excellent potential for increasing the ability to differentiate normal and pathological states.     

Semiquantifying regional cerebral blood flow by 123I-amphetamine (IMP) SPECT in cerebrovascular disorders: correlations with CBF indices by 133Xe inhalation method

To examine the capacity of detecting regional cerebral blood flow (rCBF) disturbances in stroke, measurements with 133Xe inhalation and 123I-amphetamine (IMP) SPECT were performed within 1-2 days in 19 patients. IMP SPECT images in transverse sections consisting of outer and inner areas were correlated with 32 regions of 133Xe rCBF. 133Xe rCBF was assessed by ISI, CBF15, and F1. Inter hemispheric ratio correlation showed outer IMP uptake correlated better with 133Xe CBF indices than the inner one. With higher ratios of 133Xe rCBF. IMP uptake ratios were variable, suggesting less usefulness of this parameter in evaluation of mild ischemia. Values of IMP in outer regional hypo and hyperemic areas correlated better with those of 133Xe rCBF than the inner ones. In regional ratios of hypo and hyperemic areas from hemispheric mean, outer IMP uptake correlated with 133Xe CBF indices, reflecting regional disturbances of fast clearing tissue perfusion. Regression lines between ratios in 133Xe CBF and IMP uptake were located below one to one correlation, and dissociated more for hyperemic regions. IMP SPECT correlated better with 133Xe rCBF for tissues with reduced perfusion but underestimated hyperemic regions as measured with the 133Xe method. The data suggest outer cerebral IMP uptake evaluated by SPECT could reflect flow disturbances in the brain cortex.     

Memory functions and rCBF (99m)Tc-HMPAO SPET: developing diagnostics in Alzheimer's disease

Alzheimer's disease (AD) is a primary degenerative disease of the brain. The prevalence increases with age, with devastating consequences for the individual and society. The aim of this study was to evaluate whether patients with early AD show an altered regional cerebral blood flow (rCBF) compared with control persons. Furthermore, we aimed to investigate the correlation between rCBF in sublobar volumes of the brain and performance on memory tests. Memory tests were chosen to evaluate episodic and semantic memory. Fourteen patients (aged 75.2+/-8.8 years) with early AD and 15 control persons (aged 71.4+/-3.2 years) were included. rCBF measurements with single-photon emission tomography (SPET) using technetium-99m hexamethylpropylene amine oxime (HMPAO) were performed. The rCBF (99m)Tc-HMPAO SPET images were spatially transformed to fit a brain atlas and normalised for differences in rCBF (Computerised Brain Atlas software). Cortical and subcortical volumes of interest (VOIs) were analysed and compared. Compared with the controls, AD patients showed a significantly lower rCBF ratio in temporoparietal regions, including the left hippocampus. The diagnostic sensitivity and specificity for AD were high in temporoparietal regions. AD patients had significantly reduced performance on semantic and, in particular, episodic memory tests compared with age-matched normative data, and their performance on several episodic tests correlated with rCBF ratios in parietal and temporal regions, including the left hippocampus. The correlation between rCBF ratio and level of episodic memory performance suggests that abnormalities in rCBF pattern underlie impaired episodic memory functioning in AD.     

Optimization of xenon-enhanced CT studies: beam energy, enhancement, root mean square deviation, and repeatability

The effects of varying beam energy on the computed tomographic (CT) enhancement-to-noise (S:N) ratio were studied experimentally with the DeltaScan 2020 and GE 8800 CT scanners and a 20-cm-diameter cyclindrical Plexiglas phantom containing 11 50 ml syringes filled with varying amounts of xenon and iodine. Enhancements of 54.2, 36.7, and 31.7 Hounsfield units (H)/mg l/ml were measured with the DeltaScan 2020 at 70, 100, and 120 kVp, respectively, with corresponding root mean square deviations (RMSDs) of 12, 7, and 5 H for 400 mAs scans. For the GE 8800, enhancements of 48.3, 37.6, and 32.7 H/mg l/ml were measured at 80, 100, and 120 kVp with RMSDs of 13, 8, and 7 H for 9.6 sec 320 mA scans (3.3 msec pulse). RMSD was independent of enhancement over the range of iodine concentrations studied (0-1.5 mg l/ml) and was only a weak function of region-of-interest (ROI) size. For repeated scans with the DeltaScan 2020, measurements in 17 X 17 pixel regions were reproducible to within 0.8 H for all techniques and a drift in calibration of less than 6% was observed after 8 months of clinical use. For both the DeltaScan 2020 and the GE 8800, at the milliamperage studied, lower-energy techniques offered no advantage over 120 kVp technique for xenon CT measurements of regional cerebral blood flow, which are feasible using either of these scanners.     

Brain perfusion CT compared with 15O-H2O PET in patients with primary brain tumours

Purpose

Perfusion CT (PCT) measurements of regional cerebral blood flow (rCBF) have been proposed as a fast and easy method for identifying angiogenically active tumours. In this study, quantitative PCT rCBF measurements in patients with brain tumours were compared to the gold standard PET rCBF with ¹⁵O-labelled water (¹⁵O-H₂O).

Methods

On the same day within a few hours, rCBF was measured in ten adult patients with treatment-na?ve primary brain tumours, twice using ¹⁵O-H₂O PET and once with PCT performed over the central part of the tumour. Matching rCBF values in tumour and contralateral healthy regions of interest were compared.

Results

PCT overestimated intratumoural blood flow in all patients with volume-weighted mean rCBF values of 28.2?±?18.8?ml min^?1 100?ml^?1 for PET and 78.9?±?41.8?ml min^?1 100?ml^?1 for PCT. There was a significant method by tumour grade interaction with a significant tumour grade rCBF difference for PCT of 32.9?±?15.8?ml?min^?1 100?ml^?1 for low-grade (WHO I + II) and 81.5?±?15.4?ml?min^?1 100?ml^?1 for high-grade (WHO III + IV) tumours, but not for PET. The rCBF PCT and PET correlation was only significant within tumours in two patients.

Conclusion

Although intratumoural blood flow measured by PCT may add valuable information on tumour grade, the method cannot substitute quantitative measurements of blood flow by PET and ¹⁵O-H₂O PET in brain tumours.