Differences in Hemodynamic Alteration between Atherosclerotic Occlusive Lesions and Moyamoya Disease: A Quantitative 15O-PET Study.

To clarify the differences in hemodynamic status between atherosclerotic steno-occlusive lesions (SOL) and moyamoaya disease (MMD), hemodynamic parameters were compared using 15O-PET. Twenty-four patients with unilateral SOL (67 ± 11 y) and eighteen with MMD (33 ± 16 y) were assigned to this study. MMD patients were divided into twelve unilateral and six bilateral lesions. All patients underwent 15O-PET to measure cerebral blood flow (CBF), blood volume (CBV), oxygen extraction fraction (OEF), and metabolic rate (CMRO2). Acetazolamide was administered after the baseline scan and the second 15O-water PET was performed to evaluate cerebrovascular reactivity (CVR). For the CBF calculation in 15O-water PET, the three-weighted integral method was applied based on a one-tissue compartment model with pixel-by-pixel delay correction to measure precise CBF and arterial-to-capillary blood volume (V0). Baseline hemodynamic parameters showed significantly lower CBF, V0, and CMRO2, but greater CBV, OEF, and delay (p < 0.01) in the affected hemispheres than in the unaffected hemispheres. After ACZ administration, both hemispheres showed a significant increase in CBF (p < 0.0001), but not in V0. CVR differed significantly between the hemispheres. The arterial perfusion pressure of the functioning arterial part tended to be reduced after acetazolamide administration in patients with past neurologic events caused by hemodynamic impairment. MMD patients showed greater inactive vascular and venous volumes compared with common atherosclerotic SOL patients. The hemodynamic status of cerebral circulation may vary according to the chronic process of steno-occlusive change and the development of collateral circulation. In order to evaluate physiologic differences between the two diseases, 15O-PET with an acetazolamide challenge test is useful.

Validation of T2 -based oxygen extraction fraction measurement with 15 O positron emission tomography.

PURPOSE: To evaluate the accuracy of T2 -based whole-brain oxygen extraction fraction (OEF) estimation by comparing it with gold standard 15 O-PET measurements. METHODS: Sixteen healthy adult subjects underwent MRI and 15 O-PET OEF measurements on the same day. On MRI, whole-brain OEF was quantified by T2 -relaxation-under-spin-tagging (TRUST) MRI, based on subject-specific hematocrit. The TRUST OEF was compared to the whole-brain averaged OEF produced by 15 O-PET. Agreement between TRUST and 15 O-PET whole-brain OEF measurements was examined in terms of intraclass correlation coefficient (ICC) and in absolute OEF values. In a subset of 10 subjects, test-retest reproducibility of whole-brain OEF was also evaluated and compared between the two modalities. RESULTS: Across the 16 subjects, the mean whole-brain OEF of TRUST and 15 O-PET were 36.44 ± 4.07% and 36.45 ± 3.65%, respectively, showing no difference between the two modalities (P = .99). TRUST whole-brain OEF strongly correlated with that of 15 O-PET (N = 16, ICC = 0.90, P = 4 × 10-7 ). The coefficient-of-variation of TRUST and 15 O-PET whole-brain OEF measurements were 1.79 ± 0.67% and 2.06 ± 1.55%, respectively, showing no difference between the two modalities (N = 10, P = .64). Further analyses on the effect of hematocrit revealed that correlation between PET OEF and TRUST OEF with assumed hematocrit remained significant (ICC = 0.8, P < 2 × 10-5 ). CONCLUSION: Whole-brain OEF measured by TRUST was in excellent agreement with gold standard 15 O-PET, with highly comparable accuracy and reproducibility. These findings suggest that TRUST MRI can provide accurate quantification of whole-brain OEF noninvasively.

Arterial spin labeling magnetic resonance imaging at short post-labeling delay reflects cerebral perfusion pressure verified by oxygen-15-positron emission tomography in cerebrovascular steno-occlusive disease.

BACKGROUND: Arterial transit time correction by data acquisition with multiple post-labeling delays (PLDs) or relatively long PLDs is expected to obtain more accurate imaging in cases of the cerebrovascular steno-occlusive disease. However, there have so far been no reports describing the significance of arterial spin labeling (ASL) images at short PLDs regarding the evaluation of cerebral circulation in ischemic cerebrovascular disease. PURPOSE: To clarify the role of short-PLD ASL in cerebrovascular steno-occlusive disease. MATERIAL AND METHODS: Fifty-three patients with cerebrovascular steno-occlusive disease were included in this study. All patients underwent ASL magnetic resonance imaging and 15O-PET within two days of each modality. To compare the ASL findings with each parameter of PET, the right-to-left (R/L) ratio, defined as the right middle cerebral artery (MCA) value/left MCA value, was calculated. RESULTS: There is a significant correlation between the ASL images at a short PLD and the ratio of cerebral blood flow and cerebral blood volume by 15O-PET, which may accurately reflect the cerebral perfusion pressure. A receiver operating characteristic curve analysis indicated that ASL images at PLD 1000 and 1500 ms were more accurate than at PLD 2000-3000 ms for the detection of a ≥10% change in the PET cerebral blood flow. CONCLUSION: ASL images at shorter PLDs may be useful at least as a screening modality to detect the changes in the cerebral circulation in cerebrovascular steno-occlusive disease. We must evaluate ASL images at multiple PLDs while considering the arterial transit time of each case at present.

Noninvasive method for measurement of cerebral blood flow using O-15 water PET/MRI with ASL correlation.

PURPOSE: A noninvasive image derived input function (IDIF) method was applied to estimate arterial input function from brain H215O-PET/MRI images for the measurement of cerebral blood flow (CBF) because of difficulty in arterial blood sampling during PET/MRI scans. To evaluate accuracy and reproducibility of radioactivity in the internal carotid arteries (ICA) for the IDIF method, a new phantom using a skull bone was applied in the cross-calibration process between the scanner and a gamma-well counter. METHODS: Eleven healthy volunteers (9 males, 43.9 ±â€¯10.9y) underwent PET/MRI studies with a 3-min H215O-PET and several MRI scans including arterial spin labeling (ASL) perfusion MRI. PET images were reconstructed as dynamic data using two sets of reconstruction parameters, which were determined by basic assessment of radioactivity concentration reproducibility in the tubes of the phantom. The IDIF method extracted the time-activity curves of the ICA from several image slices in the PET data. CBF images were calculated using the autoradiographic (ARG) method and a one-tissue compartment model (1-TCM). RESULTS: The global means of CBF from the ARG, 1-TCM, and ASL-MRI were 44.8 ±â€¯4.3, 47.9 ±â€¯5.9 and 57.9 ±â€¯8.6 (mL/min/100 g), respectively. CBF from ASL-MRI was significantly greater compared with CBF from H215O-PET (P < 0.001). However, these CBF values were significantly correlated with each other in the scatter plots (P < 0.05). CONCLUSIONS: Noninvasive measurement of CBF using H215O-PET/MRI and IDIF with the cross-calibration method with a skull phantom experiment provided reasonable quantitative values. The IDIF method allowed reliable estimation of arterial radioactivity concentration, which is useful for clinical application. The ASL-MRI perfusion image from the simultaneous acquisition tended to overestimate CBF.

Evaluation of the default-mode network by quantitative 15O-PET: comparative study between cerebral blood flow and oxygen consumption.

OBJECTIVE: Resting-state functional MRI (rs-fMRI) has revealed the existence of a default-mode network (DMN) based on spontaneous oscillations of the blood oxygenation level-dependent (BOLD) signal. The BOLD signal reflects the deoxyhemoglobin concentration, which depends on the relationship between the regional cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO2). However, these two factors cannot be separated in BOLD rs-fMRI. In this study, we attempted to estimate the functional correlations in the DMN by means of quantitative 15O-labeled gases and water PET, and to compare the contribution of the CBF and CMRO2 to the DMN. METHODS: Nine healthy volunteers (5 men and 4 women; mean age, 47.0 ± 1.2 years) were studied by means of 15O-O2, 15O-CO gases and 15O-water PET. Quantitative CBF and CMRO2 images were generated by an autoradiographic method and transformed into MNI standardized brain template. Regions of interest were placed on normalized PET images according to the previous rs-fMRI study. For the functional correlation analysis, the intersubject Pearson's correlation coefficients (r) were calculated for all pairs in the brain regions and correlation matrices were obtained for CBF and CMRO2, respectively. We defined r > 0.7 as a significant positive correlation and compared the correlation matrices of CBF and CMRO2. RESULTS: Significant positive correlations (r > 0.7) were observed in 24 pairs of brain regions for the CBF and 22 pairs of brain regions for the CMRO2. Among them, 12 overlapping networks were observed between CBF and CMRO2. Correlation analysis of CBF led to the detection of more brain networks as compared to that of CMRO2, indicating that the CBF can capture the state of the spontaneous activity with a higher sensitivity. CONCLUSIONS: We estimated the functional correlations in the DMN by means of quantitative PET using 15O-labeled gases and water. The correlation matrix derived from the CBF revealed a larger number of brain networks as compared to that derived from the CMRO2, indicating that contribution to the functional correlation in the DMN is higher in the blood flow more than the oxygen consumption.

Pixel-by-pixel precise delay correction for measurement of cerebral hemodynamic parameters in H215O PET study.

OBJECTIVE: A new method of delay time estimation was proposed to measure precise cerebral blood flow (CBF) and arterial-to-capillary blood volume (V 0) using 15O-water PET. METHODS: Nineteen patients with unilateral arterial stenoocclusive lesions were studied to evaluate hemodynamic status before treatment. The delay time of each pixel was calculated using least squares fitting with an arterial blood input curve adjusted to the internal carotid artery counts at the skull base. Pixel-by-pixel delay estimation provided a delay map image that could be used for precise calculation of CBF and V 0 using a one-tissue compartment model, and the values from this method were compared with those from the slice-by-slice correction method. RESULTS: The affected side showed a longer delay time than the contralateral cerebral hemisphere. Although the mean cortical CBF values were not different between the two methods, the slice-by-slice delay correction overestimated CBF in the hypo perfused area. The scatter plot of V 0 pixel values showed significant difference between the two correction methods where the slice-by-slice delay correction significantly overestimated V 0 in the whole brain (P < 0.05). CONCLUSION: Pixel-by-pixel delay correction provides delay images as well as better estimation of CBF and V 0, thus offering useful and beneficial information for the treatment of cerebrovascular disease.

Acute deep brain stimulation changes in regional cerebral blood flow in obsessive-compulsive disorder.

OBJECTIVE Deep brain stimulation (DBS) is a reversible, nonlesion-based treatment for patients with intractable obsessive-compulsive disorder (OCD). The first studies on DBS for OCD stimulating the ventral capsule/ventral striatum (VC/VS) yielded encouraging results for this neuroanatomical site's therapeutic efficacy. This investigation was conducted to better understand which regions of the cortico-striatal-thalamic-cortical network were acutely affected by VC/VS DBS for OCD. Furthermore, the objective was to identify which brain regions demonstrated changes in perfusion, as stimulation was applied across a dorsoventral lead axis that corresponded to different anatomical locations in the VC/VS. METHODS Six patients receiving VC/VS DBS for OCD underwent oxygen-15 positron emission tomography (15O-PET) scanning. Monopolar DBS was delivered at each of the 4 different electrodes on the stimulating lead in the VC/VS. The data were analyzed using SPM5. Paired t-tests were run in SPSS to identify significant changes in regional cerebral blood flow (rCBF) between stimulation conditions. Pearson's r correlations were run between these significant changes in rCBF and changes in OCD and depressive symptom severity. RESULTS Perfusion in the dorsal anterior cingulate cortex (dACC) significantly increased when monopolar DBS was turned on at the most ventral DBS contact, and this increase in dACC activity was correlated with reductions in depressive symptom severity (r(5) = -0.994, p = 0.001). Perfusion in the thalamus, striatum, and globus pallidus significantly increased when DBS was turned on at the most dorsal contact. CONCLUSIONS DBS of the VC/VS appears to modulate activity in the regions implicated in the pathophysiology of OCD. Different regions in the cortico-striatal-thalamic-cortical circuit showed increased perfusion based on whether the stimulation was more ventral or dorsal along the lead axis in the VC/VS. Evidence was found that DBS at the most ventral site was associated with clinical changes in depressive symptom severity, but not OCD symptom severity.

Assessment of oxidative metabolism in brown fat using PET imaging.

OBJECTIVE: Although it has been believed that brown adipose tissue (BAT) depots disappear shortly after the perinatal period in humans, positron emission tomography (PET) imaging using the glucose analog ¹8F-deoxy-d-glucose (FDG) has shown unequivocally the existence of functional BAT in humans, suggesting that most humans have some functional BAT. The objective of this study was to determine, using dynamic oxygen-15 (¹5O) PET imaging, to what extent BAT thermogenesis is activated in adults during cold stress and to establish the relationship between BAT oxidative metabolism and FDG tracer uptake. METHODS: Fourteen adult normal subjects (9F/5M, 30 ± 7 years) underwent triple oxygen scans (H2¹5O, C¹5O, ¹5O2) as well as indirect calorimetric measurements at both rest and following exposure to mild cold (16°C). Subjects were divided into two groups (BAT+ and BAT-) based on the presence or absence of FDG tracer uptake (SUV > 2) in cervical-supraclavicular BAT. Blood flow and oxygen extraction fraction (OEF) was calculated from dynamic PET scans at the location of BAT, muscle, and white adipose tissue (WAT). The metabolic rate of oxygen (MRO2) in BAT was determined and used to calculate the contribution of activated BAT to daily energy expenditure (DEE). RESULTS: The median mass of activated BAT in the BAT+ group (5F, age 31 ± 8) was 52.4 g (range 14-68 g) and was 1.7 g (range 0-6.3 g) in the BAT - group (5M/4F, age 29 ± 6). Corresponding SUV values were significantly higher in the BAT+ as compared to the BAT- group (7.4 ± 3.7 vs. 1.9 ± 0.9; p = 0.03). Blood flow values in BAT were significantly higher in the BAT+ group as compared to the BAT- group (13.1 ± 4.4 vs. 5.7 ± 1.1 ml/100 g/min, p = 0.03), but were similar in WAT (4.1 ± 1.6 vs. 4.2 ± 1.8 ml/100 g/min) and muscle (3.7 ± 0.8 vs. 3.3 ± 1.2 ml/100 g/min). Moreover, OEF in BAT was similar in the two groups (0.56 ± 0.18 in BAT+ vs. 0.46 ± 0.19 in BAT-, p = 0.39). Calculated MRO(2) values in BAT increased from 0.95 ± 0.74 to 1.62 ± 0.82 ml/100 g/min in the BAT+ group and were significantly higher than those determined in the BAT- group (0.43 ± 0.27 vs. 0.56 ± 0.24, p = 0.67). The DEE associated with BAT oxidative metabolism was highly variable in the BAT+ group, with an average of 5.5 ± 6.4 kcal/day (range 0.57-15.3 kcal/day). CONCLUSION: BAT thermogenesis in humans accounts for less than 20 kcal/day during moderate cold stress, even in subjects with relatively large BAT depots. Furthermore, due to the large differences in blood flow and glucose metabolic rates in BAT between humans and rodents, the application of rodent data to humans is problematic and needs careful evaluation.

Evaluation of Endothelium-dependent Myocardial Perfusion Reserve in Healthy Smokers: Cold Pressor Test using H2 (15) O PET / 대한핵의학회잡지

PURPOSE: Much evidence suggests long-term cigarette smoking alters coronary vascular endothelial response. In this study, we applied nonnegative matrix factorization (NMF), an unsupervised learning algorithm, to CO-less H2 (15) O-PET to investigate coronary endothelial dysfunction caused by smoking noninvasively. MATERIALS AND METHODS: This study enrolled eighteen young male volunteers consisting of 9 smokers (23.8 +/- 1.1 yr; 6.6 +/- 2.5 pack-years) and 9 nonsmokers (23.8 +/- 2.9 yr). They do not have any cardiovascular risk factor or disease history. Myocardial H2 (15) O-PET was performed at rest, during cold (5degrees C) pressor stimulation and during adenosine infusion. Left ventricular blood pool and myocardium were segmented on dynamic PET data by NMF method. Myocardial blood flow (MBF) was calculated from input and tissue functions by a single compartmental model with correction of partial volume and spillover effects. RESULTS: There were no significant difference in resting MBF between the two groups (Smokers: 1.43 0.41 ml/g/min and non-smokers: 1.37 +/- 0.41 ml/g/min; p = NS). during cold pressor stimulation, MBF in smokers was significantly lower than that in non-smokers (1.25 +/- 0.34 ml/g/min vs 1.59 +/- 0.29 ml/g/min ; p=0.019). The difference in the ratio of cold pressor MBF to resting MBF between the two groups was also significant (p=0.024; 90 +/- 24% in smokers and 122 +/- 28% in non-smokers.). During adenosine infusion, however, hyperemic MBF did not differ significantly between smokers and non-smokers (5.81 +/- 1.99 ml/g/min vs 5.11 +/- 1.31 ml/g/min ; p=NS). CONCLUSION: In smokers, MBF during cold pressor stimulation was significantly lower compared with nonsmokers, reflecting smoking-induced endothelial dysfunction. However, there was no significant difference in MBF during adenosine-induced hyperemia between the two groups.

Functional Brain Mapping Using H2 15O Positron Emission Tomography ( I ): Statistical Parametric Mapping Method / 대한핵의학회잡지

PURPOSE: We investigated the statistical methods to compose the functional brain map of human working memory and the principal factors that have an effect on the methods for localization. MATERIALS AND METHODS: Repeated PET scans with successive four tasks, which consist of one control and three different activation tasks, were performed on six right-handed normal volunteers for 2 minutes after bolus injections of 925 MBq H0 at the intervals of 30 minutes. Irnage data were analyzed using SPM96 (Statistical Parametric Mapping) imple-mented with Matlab (Mathworks Inc., U.S.A.). Images from the same subject were spatially registered and were normalized using linear and nonlinear transformation methods. Significant difference between control and each activation state was estimated at every voxel based on the general linear model. Differences of global counts were removed using analysis of covariance (ANCOVA) with global activity as covariate. Using the mean and variance for each condition which was adjusted using ANCOVA, t-statistics was performed on every voxel To interpret the results more easily, t-values were transformed to the standard (saussian distri-bution (Z-score). RESULTS: All the subjects carried out the activation and control tests successfully. Average rate of correct answers was 95%. The numbers of activated blobs were 4 for verbal memory I, 9 for verbal memory II, 9 for visual memory, and 6 for canjunctive activation of these three tasks. The verbal working memory activates predominantly left-sided slruetures, and the visual memory activates the right hernisphere. CONCLUSION: We conclude that rCBF PET imaging and statistical parametric mapping method were useful in the localization of the brain regions for verbal and visual working memory.