Quantification of cerebral blood flow with 99mTc-ECD SPECT based on a 3-compartment model

In the present study we developed a method for quantifying regional cerebral blood flow (rCBF) using 99mTc-ECD SPECT based on a 3-compartment model. The dynamic SPECT scanning and sequential sampling of arterial blood were performed on 12 subjects with cerebrovascular diseases and etc. We defined brain fractionation index (BFI) as a parameter of rCBF, which was obtained from a single SPECT data and arterial input. The relationship between the values of BFI and rCBF obtained by the 133Xe inhalation method was analyzed by approximation with exponential function. In this method, rCBF was calculated from the values of BFI using the inverse function of the exponential function as a regression curve. The method was applied seven other patients with cerebrovascular diseases and the values of rCBF were compared with those obtained by the 133Xe inhalation method. We observed a good correlation (r = 0.854), and the inclination was approximately 1. This method can be applied to not only large field SPECT cameras but also conventional SPECT cameras.     

Noninvasive quantification of iodine-123-iomazenil SPECT

The feasibility of a noninvasive method for quantification of [123I]iomazenil binding using a standardized arterial input function and a single venous blood sample was assessed in normal volunteers. METHODS: Serial SPECT images and blood data from six healthy male volunteers after intravenous injection of [123I]iomazenil were used. The standardized input function was derived by averaging the six subjects' arterial curves. Individual input functions were estimated by calibrating the standardized input function with one-point venous blood radioactivity concentration. Ligand transport (K1) and receptor binding were computed from the estimated input functions and two separate SPECT scans using a table look-up procedure based on a three-compartment, two-parameter model. Reference values for K1 and receptor binding were determined from the serial SPECT data and individual arterial curves using a three-compartment, three-parameter model and curve fitting. RESULTS: Analyses of the error caused by the calibration in relation to the time postinjection revealed that the optimal calibration time was 30 min postinjection. Receptor binding obtained by this simplified method correlated well with the reference values (r = 0.941) and was estimated within an error of 10% in the cerebral cortical regions. Although the estimated K1 showed relatively poor correlation (r = 0.699) with the reference value, it was an excellent relative measure in each subject. CONCLUSION: Our method provided an absolute measure of the benzodiazepine receptor binding and a relative measure of ligand transport from two SPECT scans and a venous blood sample. This method would be useful for quantitative assessment of benzodiazepine receptors in clinical settings.     

Comparison of technetium-99m-ECD to Xenon-133 SPECT in normal controls and in patients with mild to moderate regional cerebral blood flow abnormalities

Technetium-99m-1,1-ethyl cysteinate dimer (ECD) has been proposed as a "chemical microsphere" for SPECT measurement of regional cerebral blood flow (rCBF). However, its distribution has not yet been compared in humans to an established rCBF measure. Therefore, we compared the uptake and distribution of ECD with rCBF measured by 133Xe SPECT in subjects with mild to moderate flow abnormalities and in normal volunteers. Blood and urine chemistries and vital signs were unchanged from pre-ECD values up to seven days postinjection. Profile plots demonstrated pattern agreement between rCBF ratios (133Xe) and ECD count density ratios. A significant correlation of rCBF ratios to ECD count density ratios was observed (r = 0.77), with a slope of 0.64 and intercept of 0.36. To explore whether or not the relationship between rCBF and ECD was dependent on absolute flow, ECD region of interest data were expressed in units of ml/min/100 g by equating global CBF (133Xe) and ECD global count density. A closer correlation (r = 0.88) was found for these data than for the count ratio data. The slope was closer to one (m = 0.83) and the intercept was closer to zero (b = 8.2). Also, a significant correlation was observed between ECD-derived rCBF and 133Xe rCBF in the lesion area (r = 0.92) for patients with well-demarcated rCBF lesions. The slope (0.80) suggested a slight underestimation of lesion flow by ECD. Finally, ECD clearance from cortical gray matter ROIs derived from high-resolution scans from 1 to 4 hr postinjection was slow (2.4%/hr). In summary, ECD is a safe and effective marker of regional cerebral perfusion. The distribution of ECD is linearly related to rCBF measured by 133Xe SPECT, although our data suggest a mild underestimation of flow at the high end of the normal range.     

A comparative study of simple methods to measure regional cerebral blood flow using iodine-123-IMP SPECT

The aim of this study was to compare the accuracy and reliability of simple methods of quantifying regional cerebral blood flow (rCBF) with 123I-labeled N-isopropyl-p-iodoamphetamine (IMP) and SPECT and to determine which method was best. METHODS: Four methods were examined: (a) the microsphere method with continuous withdrawal of arterial blood, which was based on a microsphere model using the SPECT image obtained 5 min after tracer injection, (b) the microsphere method with one-point sampling, which was the same as the first method except that one-point sampling was used instead of continuous withdrawal, (c) the modified microsphere method with one-point sampling, which was the same as the second method except that a later SPECT image (30-min postinjection) with correction was used and (d) a table look-up method based on a two-compartment model with one-point arterial blood sampling and two SPECT scans obtained 40- and 180-min postinjection. The accuracy of these methods was validated by comparing the rCBF values with those obtained by nonlinear least squares fitting analysis based on the two-compartment model in 15 subjects. RESULTS: Regional cerebral blood flow values obtained by the first method correlated most closely with those obtained by nonlinear least squares fitting analysis (error, 6.8%). The second method estimated rCBF with a mean error of 10.4%. The third method estimated rCBF with a mean error of 13.1%, even though it tended to slightly overestimate rCBF. The fourth method was inclined to underestimate rCBF with a mean error of 17.1%, and it greatly overestimated regional distribution volume. CONCLUSION: The first method was the most accurate and reliable. For less invasiveness, the first method should be combined with one-point sampling instead of continuous withdrawal, which was used in the second method. When using a delayed SPECT image with a conventional SPECT scanner, the third method was considered to be superior to the fourth method.     

Quantification of cerebral blood flow with 99mTc-ECD SPECT by a single arterial or venous blood sample

The purpose of the study is to develop a simple and less invasive method for quantifying regional cerebral blood flow (rCBF) using 99mTc-ECD and SPECT. By employing a microsphere model, a new method to measure rCBF was developed, which required a single arterial or venous sample instead of continuous withdrawal of arterial blood. Using a regression line, the integral of input function of arterial blood from 0 to 30 min was inferred by activity of arterial blood sampled at time t; A(t), by activity multiplied by its octanol extraction rate; AN(t), by activity of venous blood at time t; V(t), and by activity multiplied by its octanol extraction rate; VN(t). The optimum sampling time of arterial or venous blood was examined when mean % error for inference became minimum. Consequently, minimum error of AN(6 min) was 5.5%, A(3 min) was 8.9%, VN(6 min) was 5.9%, and V(20 min) was 10.0%. Quantitative measurement of rCBF using the value of VN(6 min) was performed on other 6 subjects with dementia etc. To validate the method, 133Xe inhalation SPECT studies were also performed on the same subjects. We found a good agreement between them (r = 0.851). The presented one-point sampling methods were simple and less invasive for quantifying rCBF.     

Oramucosal delivery of LHRH: pharmacokinetic studies of controlled and enhanced transmucosal permeation

A method base on the two-compartment model was developed to measure quantitative cerebral blood flow (CBF) and partition coefficient (lambda) of IMP from dynamic SPECT and single arterial blood sampling. In this method, the linear differential equation of two-compartment model, Yokoi proposed, was employed and quantitative CBF and lambda values were measured with the standard input function calibrated by single arterial sampling. The input function was derived from the standard input function scaled by a factor determined by the single arterial blood sample. This new technique was applied to 5 normal volunteers (Ages ranged from 25 to 29 yr., average 26 yr.). The optimal time to calibrate the standard input function in the individual study and optimal the period of the upper limit time to which input function is integrated from IMP administration for analysis of the equation were determined to minimize the difference between integration of the calibrated standard input function and of the individual input function. Minimization of the difference yields an optimal calibration time (4 to 10 min after IMP administration) and the period of the upper limit time (8 to 60 min after acquisition start). Comparison of CBF and lambda values obtained by the graphical method using the calibrated standard data and individual input function were performed. It should be noted that CBF values were in good agreement between the two methods, respectively (r = 0.92, P<0.01; r = 0.72, p = 0.01). This method is easy to estimate CBF and lambda by only single arterial blood sampling and IMP dynamic SPECT, and useful for routine studies.     

Color functional images of the cerebral blood flow

Functional gamma imaging, in color, was established for regional cerebral blood flow (rCBF) using 133Xe. During 10 min after intracarotid injection of 133Xe in saline, 60 picture frames of the 133Xe clearance curve for the entire hemisphere were obtained. After nine-point smoothing, the rCBF for each of the 4,096 picture elements was calculated by two methods: the half-time method and the height-over-area method. Both the 133Xe clearance half-times and the calculated CBF values were displayed, using 13 steps of color, as functional CBF images of the brain. Images of peak count and total count were also displayed on the same frame of the color television. Forty-six studies, performed on 37 patients with various cerebral disorders, were divided into two types: diffuse and focal. In the diffuse type, a decrease in CBF was noted in cases of normal-pressure hydrocephalus; successful ventriculoperitoneal shunt operations were followed by recovery of CBF. Occlusion of the middle cerebral artery showed up as a wedge-shaped area of decreased CBF, even when the conventional brain scan looked normal. Increased perfusion to a tumor was frequently associated with decreased CBF in the rest of the lateral hemisphere; such a decrease could be improved by surgical removal of the tumor.     

Preictal SPECT in temporal lobe epilepsy: regional cerebral blood flow is increased prior to electroencephalography-seizure onset

Peri-ictal SPECT provides unique information on the dynamic changes in regional cerebral blood flow (rCBF) that occur during seizure evolution and, thus, could be useful in clarifying the poorly understood interplay of the interictal and ictal states in human focal epilepsy. The regional hyperperfusion observed on ictal SPECT is generally believed to be a consequence of electrical seizure activity. However, recent studies using invasive long-term cortical CBF monitoring have demonstrated that rCBF changes occur up to 20 min prior to ictal electroencephalography (EEG) onset. Because of apparent technical difficulties, no preictal SPECT studies have been reported so far. Therefore, we present our results on two patients with temporal lobe epilepsy in whom preictal SPECT scans were performed fortuitously under continuous video-EEG monitoring control. METHODS: Technetium-99m-hexamethyl propyleneamine oxime was injected 11 min (Patient 1) and 12 min (Patient 2) before clinical and EEG seizure onset, as documented from simultaneous video-EEG monitoring in two patients with temporal lobe epilepsy. We obtained accurate anatomical reference of CBF changes visible on SPECT by a special coregistration technique of MRI and SPECT. RESULTS: Whereas interictal SPECT showed a hypoperfusion of the temporal lobe ipsilateral to the seizure focus, on preictal SPECT, a significant increase in rCBF in the epileptic temporal lobe could be observed. These rCBF changes were not accompanied by any significant changes of the ongoing EEG. CONCLUSION: Our study provides evidence that rCBF is increased in the epileptic temporal lobe several minutes before EEG seizure onset. Thus, rCBF changes observed on peri-ictal SPECT scan cannot be considered a mere consequence of EEG seizure activity but may rather reflect a change in neuronal activity precipitating the transition from the interictal to the ictal state.     

Calculation of coronary blood flow from myocardial clearance of systemically administered 133Xe

Clearance curves for arterial and coronary-venous blood were determined after systemic left-ventricle or pulmonary-artery infections of 133Xe, paired with selective left-coronary-artery injections of 133Xe in 20 dogs with closed chest. Coronary blood flows calculated from systemic and coronary-artery injections were comparable only when a correction was made for arteriol recirculation of 133Xe following the systemic injection (r = 0.962) for left ventricle and 0.932 for pulmonary artery, paired with coronary artery). Experiments in four other dogs, verified that clearance of 133Xe from the pulmonary circulation was only about 60%. The myocardium/blood 133Xe partition coefficient, determined in vivo in ten dogs, agreed within 10% with that previously determined in vitro.     

Characteristics of patients at risk for perioperative myocardial infarction after infrainguinal bypass surgery: an exploratory study

Two numerical brain phantoms were generated in order to investigate errors which might be included in the quantitative measurement of regional CBF with use of single photon emission computed tomography (SPECT). The first phantom simulated the normal brain, and effects of the limited spatial resolution of the SPECT scanner were evaluated for 4 tracer kinetic models of the conventional microsphere model, the intra-carotid bolus injection technique of 133Xe, 133Xe Kanno-Lassen method, and the IMP-autoradiography (IMP-ARG) method. The second phantom simulated the diseased brain with middle-carotid artery (MCA) occlusion, and effects of the limited first-pass extraction fraction were investigated for the microsphere model with various permeability-surface area products. The limited spatial resolution caused systematic underestimation of the radioactivity concentration in the gray matter regions, and systematic overestimation in the low CBF regions. These errors in the original radioactivity distribution were found to cause further systematic errors in the calculated regional CBF images. It was also found that these errors were highly dependent on the tracer kinetic model employed, e.g., regional CBF values were overestimated in the clearance and the Kanno-Lassen methods compared with the conventional microsphere method, whereas values were underestimated in the IMP-ARG method. It was also shown in this study that the limited first-pass extraction fraction caused significant underestimation in the calculated rCBF values. In addition, regional contrast can be reduced when using a tracer with small PS product.(ABSTRACT TRUNCATED AT 250 WORDS)     

99mTc-HMPAO SPECT of the brain in mild to moderate traumatic brain injury patients: compared with CT--a prospective study

Single photon emission computed tomography (SPECT) with Technetium-99m hexamethyl propylenamine oxime (Tc-99m-HMPAO) was used in 20 patients with mild to moderate traumatic brain injury (TBI) to evaluate the effects of brain trauma on regional cerebral blood flow (rCBF). SPECT scan was compared with CT scan in 16 patients. SPECT showed intraparenchymal differences in rCBF more often than lesions diagnosed with CT scans (87.5% vs. 37.5%). In five of six patients with lesions in both modalities, the area of involvement was relatively larger on SPECT scans than on CT scans. Contrecoup changes were seen in five patients on SPECT alone, two patients with CT alone and one patient had contrecoup lesions on CT and SPECT. Of the eight patients (50%) with skull fractures, seven (43.7%) had rCBF findings on SPECT scan and five (31.3%) demonstrated decrease in rCBF in brain underlying the fracture. All these patients with fractures had normal brain on CT scans. Conversely, extra-axial lesions and fractures evident on CT did not visualize on SPECT, but SPECT demonstrated associated changes in rCBF. Although there is still lack of clinical and pathological correlation, SPECT appears to be a promising method for a more sensitive evaluation of axial lesions in patients with mild to moderate TBI.     

Regional cerebral blood flow in pediatric moyamoya disease: age-dependent decline in specific regions

Thirteen pediatric patients (ages 4-13 years) who underwent surgical treatment were examined regarding their rCBF in the preoperative periods. The postoperative rCBF was measured 39 times in these 13 patients. Thirteen healthy normal subjects (ages from 6 to 21 years) were also examined. The rCBF in the operculum and in the frontal, parietal, and occipital lobes was measured with 133Xe inhalation method and single photon emission computed tomography. In the parietal and occipital lobes, the preoperative rCBF had a negative and significant correlation with their ages, but not in the operculum or frontal lobe. However, subsequent to the surgical treatment, the rCBF increased significantly in the patients 5 years old or less, and then post-operative rCBF values had significant negative correlations with age in each region.     

Extraction and retention of technetium-99m-ECD in human brain: dynamic SPECT and oxygen-15-water PET studies

The kinetic behavior of 99mTc-ethyl cysteinate dimer (99mTc-ECD) in the human brain was investigated in six normal volunteers. METHODS: Dynamic SPECT and a three-compartmental model were used to estimate the rate constants of 99mTc-ECD in normal human brain. Extraction fraction (E), retention fraction (R) and permeability surface area product (PS product) of 99mTc-ECD were calculated using the rate constants. Regional cerebral blood flow (rCBF) was measured by PET with 15O-water. RESULTS: The rate constants in the cerebral cortex were estimated as 0.307 +/- 0.021 for K1 (influx constant), 0.201 +/- 0.047 for k2 (backdiffusion rate constant), 0.547 +/- 0.103 for k3 (lipophilic-to-hydrophilic conversion constant) and 0.0028 +/- 0.0012 for k5 (rate constant from lipophilic compartment to blood) at rCBF of 0.509 +/- 0.055 ml/g/min (mean +/- s.d.). The first-pass extraction, retention fraction and PS product were calculated as 0.608 +/- 0.069, 0.734 +/- 0.047 and 0.477 +/- 0.060, respectively. The first-pass extraction of 99mTc-ECD decreased significantly with increases in rCBF. The retention fraction and PS product of 99mTc-ECD did not show significant changes within the normal range of rCBF. The net extraction of 99mTc-ECD calculated from the static SPECT image obtained from 20 to 40 min was 0.358 +/- 0.039 in the cortex. CONCLUSION: Technetium-99m-ECD has a fairly high brain extraction, and its retention fraction and PS product appear to be independent of rCBF in the healthy human brain.     

Regional cerebral blood flow determination using 133Xe and a standard rotating gamma-camera

While most of the methods for quantitative regional cerebral blood flow (rCBF) determination in man requires expensive fast devices, a method is proposed using single photon emission computed tomography with a conventional rotating gamma camera and 133Xe inhalation. It is tested using a computer simulation of a cerebral exam and a simplified CBF map as a model. The results obtained show that this method is relevant and can be tested in clinical studies.     

Carotid artery stenosis in peripheral vascular disease

We describe the implementation and validation of a combined dynamic-autoradiographic approach for measuring the regional cerebral blood flow (rCBF) with 15O-butanol. From arterial blood data sampled at a rate of 1 s and list mode data of the cerebral radioactivity accumulated over 100 s, the time shift between blood and tissue curves, the dispersion constant DC, the partition coefficient p, and the CBF were estimated by least squares fitting. Using the fit results, a pixel-by-pixel parametrization of rCBF was computed for a single 40-s (autoradiographic) 15O-butanol uptake image. The mean global CBF found in 27 healthy subjects was 49 +/- 8 ml 100 g-1 min-1. Gray and white matter rCBF were 83 +/- 20 and 16 +/- 3 ml 100 g-1 min-1, respectively, with a corresponding partition coefficient p of 0.77 +/- 0.18 and 0.77 +/- 0.29 ml/g in both compartments. The quantitative images resulted in a significantly higher gray matter rCBF than the autoradiographic images.     

Nonlinearity correction of brain perfusion SPECT based on permeability-surface area product model

It is well known that many cerebral perfusion tracers underestimate cerebral blood flow in high flow range. A model has been proposed to correct nonlinear relationship of flow and uptake of the tracers that accounts for the permeability-surface area product (PS model). METHODS: We examined 43 patients in this study. To test the feasibility of this method for 123I-IMP, 99(m)Tc-HMPAO and 99(m)Tc-ECD, radioactivity ratios of cerebral regions to cerebellum (C/Cr) on SPECT images were compared with those of rCBF (F/Fr) measured by PET using the 15O CO2 steady-state method. Coefficient for correction in the PS model was estimated by the least squares method, and SPECT data were corrected using these coefficients. RESULTS: Estimated PS value by this method was highest in IMP (116 ml/min/100 g) followed by ECD (66 ml/min/100 g) and HMPAO (46 ml/min/100 g). The corrected SPECT data demonstrated an excellent linear relationship, which was close to unity, with rCBF. CONCLUSION: These results indicate that the PS model can be used for nonlinearity correction of brain perfusion SPECT.     

Crossed cerebellar diaschisis: analysis of iodine-123-IMP SPECT imaging

The aim of this study was to review the etiology of CCD and study factors that affect the development and manifestation of CCD. METHODS: Three hundred and eleven patients with supratentorial lesions were evaluated for the presence of CCD with SPECT and 123I-IMP. In representative cases, continuous arterial blood sampling was done and rCBF was calculated using Kuhl's method. RESULTS: IMP-SPECT detected an abnormality in 206 patients, of whom 30 had CCD. Of CCD patients, 27 had more than single lobe involvement, 17 had motor impairment, 8 of 11 had rCBF of less than 29.1 +/- 10.9 ml/100 g/min. There was also a significant difference in rCBF between non-CCD and CCD cases. CONCLUSION: Although CCD can also occur with dementia (mixed or vascular type), it is more common with multilobar lesions. It is also associated with the presence of motor impairment but not related to its severity. It is more likely to develop, however, if rCBF is less than 29.1 +/- 10.9 ml/100 g/min regardless of etiology.     

Validation of a less-invasive method for measurement of serotonin synthesis rate with alpha-[11C]methyl-tryptophan

We tested in normal human subjects a less invasive method to obtain plasma input function required in the calculation of the brain serotonin synthesis rate measured with positron emission tomography (PET) and alpha-[11C]methyl-tryptophan (alpha-MTrp). The synthesis rates derived with the arterial input function were compared to those derived from venous plasma and venous sinus time-radioactivity curves obtained from dynamic PET images. Dynamic PET images were obtained for the lengths up to 90 minutes after an injection of alpha-MTrp (400 to 800 MBq). Input functions were generated from both artery and vein in three subjects, and from artery only in two subjects. Net unidirectional uptake constants of alpha-MTrp (K*; mL/g/min) were calculated in several brain regions graphically using data between 20 and 60 minutes after injection with different input functions. In the five subjects with arterial sampling, we tested two methods for correcting the input functions from the venous samples: (1) normalization to the mean exposure time at 20 minutes from arterial curve; and (2) the use of the venous sinus curve for the first 20 minutes. Venous curves coincided with the arterial ones after about 20 minutes. When the venous curves were used, there was an underestimation of the area under the curves up to 20 minutes, resulting in a 5% to 30% overestimation of K* values. Combined use of the sinus curve up to 20 minutes and venous curve from 20 to 60 minutes as an input function resulted in the K* (mL/g/min) values larger by 7.1 +/- 3.8% than the K* values estimated with the arterial input function. Normalization of the venous curve to the exposure time at 20 minutes obtained from the arterial plasma curve resulted in a bias in the K* of about -0.34 +/- 3.32%. The bias from the K* values was propagated to the serotonin synthesis rates. The use of a combination of the venous blood samples and venous sinus as the input function resulted in an acceptable bias in the serotonin synthesis rates from the tissue time-radioactivity curves generated by PET.     

Regional cerebral blood flow during the Wisconsin Card Sorting Test in normal subjects studied by xenon-133 dynamic SPECT: comparison of absolute values, percent distribution values, and covariance analysis

We studied regional cerebral blood flow (rCBF) by xenon-133 dynamic single photon emission computed tomography (SPECT) in 17 normal volunteers who were performing the Wisconsin Card Sorting Test (WCST), a task that is particularly sensitive to disturbance of the prefrontal cortex, and a simple matching-to-sample task (BAR) as a sensorimotor control. Three methods for statistical analysis of regional "subtraction" data were used: absolute rCBF values, percent distribution values, and means adjusted for global CBF changes (covariance analysis). The absolute values had high variance, due to the combination of interindividual differences in global flow and intra-individual variation, and showed no statistically significant regional changes. This variation was greatly reduced by percent values and covariance analysis, which had quite similar outcomes. With both methods, significant increases of rCBF during the WCST as compared with the BAR were seen in the right anterior dorsolateral prefrontal and left occipital cortices, and reduction of rCBF in the left pararolandic region. Moreover, significant correlations with performance were found in the medial regions of the frontal lobes, with opposite trends for the right and left hemisphere. The posterior dorsolateral prefrontal region showed a negative correlation with sensory-motor frequency, an index related to the task's difficulty. These results are consistent with previous findings using other rCBF techniques and confirm the statistical advantage of normalization and covariance methods, which yield practically identical results, at least in this analysis based on regions of interest.     

Postoperative hyperperfusion in dural arteriovenous fistula associated with venous ischemia: case report

BACKGROUND: It is well known that carotid endarterectomy and extracranial-intracranial arterial bypass sometimes cause postoperative hyperperfusion, and vasoparalysis attributable to long-standing ischemia has been suggested as the cause. It is also well known that dural arteriovenous fistula (AVF) sometimes causes cerebral ischemia attributable to venous hypertension. However, there are few reports regarding the postoperative changes of regional cerebral blood flow (rCBF). METHODS: We report a case of dural AVF of the left transverse/sigmoid sinuses, occurring in a 64-year-old man. Intraoperative transvenous embolization combined with transarterial embolization was performed, and the rCBF was measured pre- and postoperatively using 99mTc-hexamethyl-propylene amine oxime and single-photon emission computed tomography (SPECT). RESULTS: Preoperative SPECT disclosed a marked rCBF reduction in the left temporal, parietal, and occipital lobes. Complete obliteration of the AVF was attained after the intraoperative transvenous embolization, without any neurological deterioration. However, postoperative SPECT demonstrated temporary hyperperfusion in these regions. CONCLUSIONS: Sudden resolution of venous ischemia can lead to postoperative hyperperfusion, and pre- and post-treatment rCBF studies are important to prevent complications related to hyperperfusion.