Water PET Research Articles

Impaired verbal memory in Parkinson disease: relationship to prefrontal dysfunction and somatosensory discrimination

ObjectiveTo study the neurocognitive profile and its relationship to prefrontal dysfunction in non-demented Parkinson's disease (PD) with deficient haptic perception.MethodsTwelve right-handed patients with PD and 12 healthy control subjects underwent thorough neuropsychological testing including Rey complex figure, Rey auditory verbal and figural learning test, figural and verbal fluency, and Stroop test. Test scores reflecting significant differences between patients and healthy subjects were correlated with the individual expression coefficients of one principal component, obtained in a principal component analysis of an oxygen-15-labeled water PET study exploring somatosensory discrimination that differentiated between the two groups and involved prefrontal cortices.ResultsWe found significantly decreased total scores for the verbal learning trials and verbal delayed free recall in PD patients compared with normal volunteers. Further analysis of these parameters using Spearman's ranking correlation showed a significantly negative correlation of deficient verbal recall with expression coefficients of the principal component whose image showed a subcortical-cortical network, including right dorsolateral-prefrontal cortex, in PD patients.ConclusionPD patients with disrupted right dorsolateral prefrontal cortex function and associated diminished somatosensory discrimination are impaired also in verbal memory functions. A negative correlation between delayed verbal free recall and PET activation in a network including the prefrontal cortices suggests that verbal cues and accordingly declarative memory processes may be operative in PD during activities that demand sustained attention such as somatosensory discrimination. Verbal cues may be compensatory in nature and help to non-specifically enhance focused attention in the presence of a functionally disrupted prefrontal cortex.

Imaging of Cyclosporine Inhibition of P-Glycoprotein Activity Using 11C-Verapamil in the Brain: Studies of Healthy Humans

The multiple-drug resistance (MDR) transporter P-glycoprotein (P-gp) is highly expressed at the human blood-brain barrier (BBB). P-gp actively effluxes a wide variety of drugs from the central nervous system, including anticancer drugs. We have previously demonstrated P-gp activity at the human BBB using PET of (11)C-verapamil distribution into the brain in the absence and presence of the P-gp inhibitor cyclosporine-A (CsA). Here we extend the initial noncompartmental analysis of these data and apply compartmental modeling to these human verapamil imaging studies. Healthy volunteers were injected with (15)O-water to assess blood flow, followed by (11)C-verapamil to assess BBB P-gp activity. Arterial blood samples and PET images were obtained at frequent intervals for 5 and 45 min, respectively, after injection. After a 60-min infusion of CsA (intravenously, 2.5 mg/kg/h) to inhibit P-gp, a second set of water and verapamil PET studies was conducted, followed by (11)C-CO imaging to measure regional blood volume. Blood flow was estimated using dynamic (15)O-water data and a flow-dispersion model. Dynamic (11)C-verapamil data were assessed by a 2-tissue-compartment (2C) model of delivery and retention and a 1-tissue-compartment model using the first 10 min of data (1C(10)). The 2C model was able to fit the full dataset both before and during P-pg inhibition. CsA modulation of P-gp increased blood-brain transfer (K(1)) of verapamil into the brain by 73% (range, 30%-118%; n = 12). This increase was significantly greater than changes in blood flow (13%; range, 12%-49%; n = 12, P < 0.001). Estimates of K(1) from the 1C(10) model correlated to estimates from the 2C model (r = 0.99, n = 12), indicating that a short study could effectively estimate P-gp activity. (11)C-verapamil and compartmental analysis can estimate P-gp activity at the BBB by imaging before and during P-gp inhibition by CsA, indicated by a change in verapamil transport (K(1)). Inhibition of P-gp unmasks verapamil trapping in brain tissue that requires a 2C model for long imaging times; however, transport can be effectively measured using a short scan time with a 1C(10) model, avoiding complications with labeled metabolites and tracer retention.

Myocardial perfusion quantitation with 15O-labelled water PET: high reproducibility of the new cardiac analysis software (Carimas™)

Carimas (Cardiac Image Analysis System) is a new software package developed at the Turku PET Centre for the quantitation of PET studies of the heart with a broad range of tracers. The goal of this study was to assess the reproducibility of results the package provides for myocardial perfusion (MP) quantitation using (15)O-labelled water. Four observers with various levels of experience in nuclear medicine independently analysed 20 MP studies (10 rest flow: "rest", 10 adenosine-induced hyperaemia: "stress"). Each study was analysed twice. The linear mixed model for repeated measures was fitted to the data to calculate intraclass correlation coefficients (ICC), differences between the repeats (the intraobserver differences) and differences between the observers (the interobserver differences). Also, Pearson correlation coefficients (r) were calculated and Bland-Altman plots were drawn. The reproducibility of MP was assessed on global, regional and segmental levels. Thereafter, this analysis was applied in 48 consecutive clinical patients with suspected coronary heart disease (CHD). For the experienced observer the Pearson r for all segments was 0.974 at rest and 0.978 at stress (p < 0.0001), and the repeatability coefficients were 0.145 ml/g per min (15.5% of the average) and 0.389 ml/g per min (14.9%), correspondingly. The ICC reflected very good overall reproducibility. The intraobserver and interobserver differences were small, and the difference between the most and the least experienced observers at stress was 8.5% for the global MP. The clinical accuracy of the perfusion in the detection of CHD was excellent (positive predictive value 91% and negative predictive value 88%) against invasive angiography. The results demonstrate high reproducibility of myocardial perfusion quantitation with (15)O-labelled water PET using Carimas. The results support the feasibility of robust analysis and good clinical accuracy.

Metabolism-perfusion mismatch as assessed by PET varies with breast cancer phenotype and predicts response to neoadjuvant chemotherapy.

Abstract Abstract #6005 Background: Kinetic analysis of FDG and water PET can identify patterns of breast cancer metabolism and perfusion in patients receiving neoadjuvant chemotherapy (NC). Previously, we found that high pre-therapy glucose tumor metabolism relative to perfusion was associated with poor tumor pathologic response, early relapse, and death in patients with locally advanced breast cancer (LABC) treated with NC. This analysis examines tumor metabolism and perfusion as a function of tumor phenotype. Material and Methods: Tumor phenotype, defined by immunohistochemistry (IHC), was determined in 51 patients undergoing NC between 1995 and 2005. Luminal tumors were defined as those expressing either estrogen receptor (ER) or progesterone receptor (PR). The triple-negative (TN) phenotype was defined as ER and PR negative without HER2 overexpression by IHC or amplification by FISH. HER2 phenotype showed HER2 overexpression or amplification but were ER/PR negative. Women with LABC underwent dynamic [18F]-FDG and [15O]-water PET scans prior to NC. The FDG metabolic rate (MRFDG) and transport (FDG K1) parameters were calculated; blood flow (BF) was estimated from the water PET scan. Response to NC was determined from surgical specimens with pathologic complete response (pCR) defined as eradication of invasive tumor in the breast vs. other. Results: Of the tumors studied, 16 (31%) were TN, 30 (59%) were luminal, and 5 (10%) were HER2. pCR was observed in 4/16 (25%) TN tumors (95% CI: 0.10-0.50) compared to only 4/30 (13%) of luminal tumors (95% CI: 0.05-0.30) and 3/5 HER2 tumors. Linear regression of the association between PET parameters and phenotype (TN vs. luminal) found that TN was associated with higher MRFDG (p=0.007) and MRFDG/BF ratio (p=0.02), but not with BF (p=0.27). Only patients with low pre-therapy MRFDG/BF ratio (&amp;lt;35 umol/mL) achieved a pCR. Using this value as an ad-hoc cutoff, 4/7 (57%) of TN patients with low ratios had a pCR, while 0/9 with higher ratios had pCR. In contrast, only 4/21 (19%) of the luminal patients with low ratios had a pCR (one-sided mid-p=0.04 for TN vs. luminal pCR rate for patients with MRFDG/BF &amp;lt; 35 umol/mL). Discussion: These results demonstrate heterogeneity in breast tumor metabolism and perfusion as assessed by PET, and suggest a clinically relevant association between PET parameters and tumor phenotypes. The high MRFDG/BF ratio that predicts poor response to NC is more common in TN tumors; whereas in luminal or HER2 tumors, high MRFDG is generally matched with higher BF. Measurement of tumor metabolism and perfusion may identify a subset of tumors which are unlikely to respond to NC. Identification of such tumors may direct therapy toward those biologic targets most likely to overcome resistance. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6005.

Perception of pain in the minimally conscious state with PET activation: an observational study

Patients in a minimally conscious state (MCS) show restricted self or environment awareness but are unable to communicate consistently and reliably. Therefore, better understanding of cerebral noxious processing in these patients is of clinical, therapeutic, and ethical relevance. We studied brain activation induced by bilateral electrical stimulation of the median nerve in five patients in MCS (aged 18-74 years) compared with 15 controls (19-64 years) and 15 patients (19-75 years) in a persistent vegetative state (PVS) with (15)O-radiolabelled water PET. By way of psychophysiological interaction analysis, we also investigated the functional connectivity of the primary somatosensory cortex (S1) in patients and controls. Patients in MCS were scanned 57 (SD 33) days after admission, and patients in PVS 36 (9) days after admission. Stimulation intensities were 8.6 (SD 6.7) mA in patients in MCS, 7.4 (5.9) mA in controls, and 14.2 (8.7) mA in patients in PVS. Significant results were thresholded at p values of less than 0.05 and corrected for multiple comparisons. In patients in MCS and in controls, noxious stimulation activated the thalamus, S1, and the secondary somatosensory or insular, frontoparietal, and anterior cingulate cortices (known as the pain matrix). No area was less activated in the patients in MCS than in the controls. All areas of the cortical pain matrix showed greater activation in patients in MCS than in those in PVS. Finally, in contrast with patients in PVS, those in MCS had preserved functional connectivity between S1 and a widespread cortical network that includes the frontoparietal associative cortices. Cerebral correlates of pain processing are found in a similar network in controls and patients in MCS but are much more widespread than in patients in PVS. These findings might be objective evidence of a potential pain perception capacity in patients in MCS, which supports the idea that these patients need analgesic treatment.

Multivariate analysis: Applications to the study of hereditary movement disorders

Idiopathic torsion dystonia and Huntington’s disease represent autosomal dominant inherited hyperkinetic disorders that vary considerably with regard to pathologic mechanisms and clinical penetrance. To study these mechanisms, non-manifesting DYT1 mutation carriers (nmDYT1) and presymptomatic HD gene carriers (p-HD), as well as age-matched controls were scanned with (i) FDG PET in the resting state, and (ii) 15O-labeled water PET while performing a motor sequence learning task and motor execution task. We used voxel-based principal components analysis (PCA) to isolate the effects of genotype on regional metabolism in the resting state and on patterns of activation during motor performance. We detected two specific genotype-related metabolic patterns in the resting state. The torsion dystonia-related pattern was characterized by hypermetabolism of the basal ganglia, cerebellum and the supplementary motor area (SMA). By contrast, the voxel-based HD-related pattern displayed reductions in caudate and putamen metabolic activity associated with relative increases in the thalamus, the calcarine cortex, and primary motor cortex. Both mutations were associated with sequence learning deficits compared to controls. Carriers of each genotype activated different networks while performing the sequence learning task. In nmDYT1, learning was associated with activation of a specific network involving the cerebellar hemispheres, the left pre-SMA and anterior cingulate region, as well as inferior prefrontal and occipital association cortices. In p-HD, the learning network involved activation of the orbitofrontal and occipital association regions bilaterally, the left mediodorsal thalamus, and the right cerebellar hemisphere. These topographies illustrate the utility of PCA in identifying functional abnormalities in fronto-striatal loops and related pathways.

Assessment of myocardial perfusion by dynamic O-15–labeled water PET imaging: Validation of a new fast factor analysis

Factor analysis (FA) is an established method for separating myocardium from blood pool by use of oxygen 15-labeled water and positron emission tomography for analyzing myocardial blood flow (MBF). Conventional FA methods generating images from sinograms (sinoFA) are time-consuming, whereas FA can be performed on the reconstructed images (reconFA) in a fraction of time. We validated the MBF values obtained by reconFA versus sinoFA. In 23 volunteers (mean age, 26.6 +/- 3.4 years) MBF was calculated from sinoFA and reconFA and blindly reanalyzed 1 month later by the same observer. Intraobserver agreement and reconFA-versus-sinoFA agreement were assessed according to Bland and Altman (BA). Reproducibility proved excellent for global sinoFA (r = 0.968; P < .001; BA limits, -0.617 to 0.676 mL x min(-1) x g(-1)) and slightly superior for reconFA (r = 0.979; P < .001; BA limits, -0.538 to 0.558 mL x min(-1) x g(-1)), with wider limits of agreement for segmental MBF from sinoFA (r = 0.777; P < .001; BA limits, -1.676 to 1.656 mL x min(-1) x g(-1)) and reconFA (r = 0.844; P < .001; BA limits, -1.999 to 1.992 mL x min(-1) x g(-1)). In addition, sinoFA and reconFA showed excellent correlation (r = 0.975, P < .001) and agreement (BA limits, -0.528 to 0.648 mL x min(-1) x g(-1)) for global and segmental values (r = 0.955; P < .001; BA limits, -1.371 to 1.491 mL x min(-1) x g(-1)). Use of reconFA allows rapid and reliable quantitative MBF assessment with O-15-labeled water.

Use of changes in blood flow PET measurements to predict post-therapy lymph node status among locally advanced breast cancer patients

575 Background: Response to neoadjuvant therapy in the primary tumor and nodal metastasis predicts benefit to patients as shown in several large clinical trials. We have previously shown that changes in tumor blood flow (BF) measured by [15O]-water PET predict pathologic primary tumor response. We now test whether primary tumor blood flow changes also predict axillary nodal metastases response and post-therapy lymph node status among women with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy. Methds: Fifty-five women with a primary diagnosis of LABC underwent dynamic [15O]-water PET scans prior to and at midpoint of neoadjuvant chemotherapy. We evaluated associations between tumor BF changes and pathologic primary tumor response: categorized as complete (CR), partial (PR) or no response (NR). We also assessed the relationship between primary tumor BF changes and post-therapy axillary lymph node status, categorizing the high risk (HR) group as 4+ nodes with extracapsular extension (ECE, n=12) versus the lower risk (LR) group with either fewer than 4+ nodes or without ECE (n=43). Results: The median changes in BF versus tumor response were: CR = -77%, PR = -40%, and, NR = +20% (P = &lt;0.001). For axillary node response, the median BF change among HR patients was +20% versus - 49% among LR patients (P = 0.004). Eight of 17 patients with an increase in tumor blood flow were HR whereas 4/38 patients with decreased tumor blood flow were HR (P = 0.002). Conclusions: Change in primary tumor blood flow over the course of neoadjuvant chemotherapy predicts pathologic response to treatment with a substantial decrease observed among CRs. An increase in primary tumor BF with treatment portends significant residual primary tumor and a nearly 50% chance of very high-risk nodal disease post-therapy. No significant financial relationships to disclose.

Correlation Between Extraversion and Regional Cerebral Blood Flow in Response to Olfactory Stimuli

Extraversion, a trait associated with individual differences in approach motivation and the experience of positive emotional states, is negatively correlated with certain psychiatric disorders, including depression and social phobia. The authors examined the correlation between extraversion and regional cerebral blood flow (rCBF) while participants were exposed to olfactory stimuli in order to further characterize individual differences in hedonic processing associated with this trait. Twelve healthy participants were exposed to pleasant and unpleasant odors while rCBF was measured using [(15)O] water PET. The NEO Five-Factor Inventory was used to assess extraversion. Associations between extraversion scores and rCBF in each olfactory stimulus condition were assessed by correlational analysis. During the pleasant smell condition, extraversion was correlated with rCBF in the amygdala and occipital cortex. During the unpleasant smell condition, extraversion was correlated with rCBF in the occipital cortex and inferior temporal gyrus. These results provide important evidence for the biological basis of extraversion and indicate that there are systematic individual differences in patterns of brain activation in response to affective stimuli.

Correlation Between Extraversion and Regional Cerebral Blood Flow in Response to Olfactory Stimuli

Objective: Extraversion, a trait associated with individual differences in approach motivation and the experience of positive emotional states, is negatively correlated with certain psychiatric disorders, including depression and social phobia. The authors examined the correlation between extraversion and regional cerebral blood flow (rCBF) while participants were exposed to olfactory stimuli in order to further characterize individual differences in hedonic processing associated with this trait. Method: Twelve healthy participants were exposed to pleasant and unpleasant odors while rCBF was measured using [ 15 O] water PET. The NEO Five-Factor Inventory was used to assess extraversion. Associations between extraversion scores and rCBF in each olfactory stimulus condition were assessed by correlational analysis. Results: During the pleasant smell condition, extraversion was correlated with rCBF in the amygdala and occipital cortex. During the unpleasant smell condition, extraversion was correlated with rCBF in the occipital cortex and inferior temporal gyrus. Conclusions: These results provide important evidence for the biological basis of extraversion and indicate that there are systematic individual differences in patterns of brain activation in response to affective stimuli.

Can the detection of misery perfusion in chronic cerebrovascular disease be based on reductions in baseline CBF and vasoreactivity?

The aim of this study was to clarify whether decreases in baseline regional cerebral blood flow (rCBF) and in residual cerebral vasoreactivity (CVR), assessed by the acetazolamide (ACZ) challenge, can detect misery perfusion in patients with chronic cerebrovascular disease (CVD). Oxygen extraction fraction (OEF) and other haemodynamic parameters were measured in 115 patients (64+/-9 years old) with unilateral cerebrovascular steno-occlusive disease (>70% stenosis) using (15)O-gas and water PET. A significant elevation of OEF, by greater than the mean+2SD compared with healthy controls, was defined as misery perfusion. CBF, CVR determined by percent change in CBF after ACZ administration, OEF and other haemodynamic parameters in the territories of the bilateral middle cerebral arteries were analysed. Diagnostic accuracy for the detection of misery perfusion using the criteria determined by baseline CBF and CVR was evaluated in all patients and in only those patients with occlusive lesions. Ten of 24 patients with misery perfusion showed a significant reduction in CVR. Using criteria determined by significant decreases in CVR and baseline CBF, misery perfusion was detected with a sensitivity of 42% and a specificity of 95% in all patients. In patients with occlusive lesions (n=50), sensitivity was higher but specificity was slightly lower. The diagnostic accuracy of the threshold determined by baseline CBF alone was similar in all patients and in only those patients with occlusive lesions, and was higher than that achieved using the asymmetry index of OEF. Reductions in CVR and baseline CBF in the ACZ challenge for CVD would detect misery perfusion with high specificity. Reduction in baseline rCBF is more accurate than reduction in CVR alone for the detection of misery perfusion.

Myocardial flow reserve is influenced by both coronary artery stenosis severity and coronary risk factors in patients with suspected coronary artery disease

Myocardial flow reserve (MFR) measurement has an important role in assessing the functional severity of coronary artery stenosis. However, a discrepancy between the anatomical severity of coronary artery stenosis and MFR is often observed. Such a discrepancy may be explained by coronary risk factors. In this study, we aimed to investigate the influence of coronary artery stenosis severity and risk factors on MFR. Seventy-four patients suspected to have coronary artery disease and seven age-matched healthy volunteers were enrolled. Myocardial blood flow (MBF) and MFR were measured using 15O-labelled water PET. Regional MFR was calculated in regions with significant coronary artery stenosis (stenotic regions) and in regions without significant stenosis (remote regions). The contributions of coronary artery stenosis severity and coronary risk factors were assessed using univariate and multivariate analyses. In stenotic regions, MFR correlated inversely with coronary artery stenosis severity (r=-0.50, p<0.01). Univariate analysis did not show any significant difference in MFR between the patients with and the patients without each risk factor. In remote regions, however, MFR was significantly decreased in the diabetes and smoking groups (each p<0.05). By multivariate analysis, diabetes and smoking were independent predictors of MFR (each p<0.05). In the group with more than one risk factor, MFR was significantly lower (2.78+/-0.79) than in the other group (3.40+/-1.22, p<0.05). MFR is influenced not only by coronary stenosis severity but also by coronary risk factors. In particular, the influence of risk factors should be considered in regions without severe coronary stenosis.

Neuroimaging as a marker of the onset and progression of Alzheimer's disease

Several neuroimaging techniques are promising tools as early markers of brain pathology in Alzheimer's disease (AD). On structural MRI, atrophy of the entorhinal cortex is present already in mild cognitive impairment (MCI). In the autosomal dominant forms of AD, the rate of atrophy of medial temporal structures separates affected from control persons even 3 years before the clinical onset of cognitive impairment. The elevated annual rate of brain atrophy offers a surrogate tool for the evaluation of newer therapies using smaller samples, thereby saving time and resources. On functional MRI, activation paradigms activate a larger area of parieto-temporal association cortex in persons at higher risk for AD, whereas the entorhinal cortex activation is lesser in MCI. Similar findings have been detected with activation procedures and water (H 2 15O) PET. Regional metabolism in the entorhinal cortex, studied with FDG PET, seems to predict normal elderly who will deteriorate to MCI or AD. SPECT shows decreased regional perfusion in limbic areas, both in MCI and AD, but with a lower likelihood ratio than PET. Newer PET compounds allow for the determination in AD of microglial activation, regional deposition of amyloid and the evaluation of enzymatic activity in the brain of AD patients.

The neural correlates of spatial language in English and American Sign Language: a PET study with hearing bilinguals

Rather than specifying spatial relations with a closed-class set of prepositions, American Sign Language (ASL) encodes spatial relations using space itself via classifier constructions. In these constructions, handshape morphemes specify object type, and the position of the hands in signing space schematically represents the spatial relation between objects. A [ 15O]water PET study was conducted to investigate the neural regions engaged during the production of English prepositions and ASL locative classifier constructions in hearing subjects with deaf parents (ASL-English bilinguals). Ten subjects viewed line drawings depicting a spatial relation between two objects and were asked to produce either an ASL locative classifier construction or an English preposition that described the spatial relation. The comparison task was to name the figure object (colored red) in either ASL or in English. Describing spatial relations in either ASL or English engaged parietal cortex bilaterally. However, an interaction analysis revealed that right superior parietal cortex was engaged to a greater extent for ASL than for English. We propose that right parietal cortex is involved in the visual–motoric transformation required for ASL. The production of both English prepositions and ASL nouns engaged Broca's area to a greater extent than ASL classifier constructions. We suggest that Broca's area is not engaged because these constructions do not involve retrieval of the name of an object or the name of a spatial relation. Finally, under the same task conditions, only left parietal activation was observed for monolingual English speakers producing spatial prepositions (H. Damasio et al., 2001, NeuroImage, 13). We conclude that the right hemisphere activation observed for ASL-English bilinguals was due to their life-long experience with spatial language in ASL.

The relationship between myocardial flow reserve and washout of Tc-99m sestamibi in patients with chronic heart failure

Backgrounds: It has been well known that Tc-99m sestamibi may have the potential for freezing myocardial perfusion. However, this agent does not freeze myocardial perfusion in a certain situation such as impaired myocardium (JNM 1996:1289–94). The abnormalities of Myocardial blood flow (MBF) and flow reserve have been observed in patients with chronic heart failure (CHF) and MBF reserve may play an important role of the prognosis in these patients. This study was designed to compare myocardial blood flow and flow reserve with washout of Tc-99m sestamibi in CHF patients. Methods: MBF and MBF reserve were measured in 10 patients with CHF due to non-ischemic cardiomyopathy and 10 control subjects by means of O-15 Water PET. Myocardial planar images were also performed using Tc-99m sestamibi in order to measure washout (WO). These parameters were compared to other CHF parameters such as ejection fraction and BNP. Results: The values of MBF reserve in CHF patients significantly decreased compared to control (1.93 + 0.39 versus 3.00 + 0.79, p<0.05), though MBF at rest did not significantly change. The WO in these patients significantly increased compared with control (34.0 + 6.3% versus 26.5 + 4.0 %, p<0.05). And in addition, the values of WO showed a significant negative correlation to MBF reserve in patients with CHF (r=-0.81). The values of WO were not correlated with ejection fraction, but with BNP (r= 0.76). Conclusions: These results indicated that both myocardial flow reserve and washout of Tc-99m sestamibi were impaired in patients with CHF, reflecting the existence of myocardial cell damage. And in addition, the washout of Tc-99m sestabmibi were closely correlated with myocardial flow reserve and BNP, suggesting the washout of Tc-99m sestamibi might be useful for the risk stratification in patients with CHF.

Adenosine-induced myocardial flow reactivity in pig as assessed with O-15 water PET

Objectives: This study was intended to evaluate the feasibility and applicability of assessing absolute myocardial blood flow (MBF) using O-15 water and PET 14 times for various doses of vasodilator challenges in miniature pigs. Methods and results: MBFs were quantitated following intravenous injection of O-15 water during various administration doses of adenosine (25–800 μg/kg/min) and A2A-selective CGS-21680 (0.5–20 μg/kg) in six miniature pigs. A low dose of adenosine increased MBF but reached to a maximum, and gradually decreased MBF with reduced heart rate (HR), reduced systolic blood pressure (SBP), and thus decreased RPP, together with prolonged PR interval. Reduction in HR, SBP and RPP were also observed with CGS-21680, but were significantly less, and the maximum MBF was greater with CGS-21680. These findings were consistent and reproducible among all the six subjects. Discussion and conclusion: The technique of assessing MBF with O-15 water and PET appeared to be reproducible and useful for quantitative evaluation of the vascular reactivity for various pharmacological/physiological stresses. The ability of accurately correcting for the partial volume effect, and recent advances of generating functional parametric images from the dynamic O-15 water alone, would be the most important factors in clinical usage of this methodology.

Experimental evaluation of iterative reconstruction versus filtered back projection for 3D [ 15O]water PET activation studies using statistical parametric mapping analysis

Iterative reconstructions are increasingly used for clinical PET studies owing to the better noise properties compared with filtered backprojection (FBP). The purpose of the present study was to compare ordered subsets expectation maximization (OSEM) iterative reconstruction with FBP as input for statistical parametric mapping (SPM) analysis of PET activation studies. Two phantom studies were performed simulating both motor and cognitive tasks and acquiring data with both high and low statistics. In contrast to clinical studies, where no a priori information is known, phantom studies allow for an accurate and detailed comparison between different reconstruction techniques. The significance of “activations” during “tasks” was determined using SPM99 software. Using region of interest analysis of SPM results, it was found that the maximum and average t values within each hot spot of the phantom were higher for OSEM than for FBP. In addition, OSEM4 × 16 (4 iterations, 16 subsets) produced fewer false-positive voxels than FBP, OSEM1 × 16 and OSEM2 × 16. In conclusion, for PET activation studies use of OSEM4 × 16 seems to give the best tradeoff between signal detection and noise reduction.

Autoregulation of blood pressure and thought: preliminary results of an application of brain imaging to psychosomatic medicine.

This presentation seeks to demonstrate the use of brain imaging techniques for understanding the interaction between hypertension and psychosocial function. The historical background for the study of brain function among hypertensive patients is reviewed. An initial and a current project examining rCBF with 15O water radiotracer and PET in unmedicated hypertensives and normotensives are described. The rCBF response is assessed during the performance of spatial and verbal working memory tasks of increasing memory load. The assessment also addresses the influence on rCBF and performance of white matter hyperintensities and the presence of carotid artery thickening. Initial results suggest that hypertensives relative to normotensives show less CBF and less posterior parietal rCBF in response to increases in memory load. Hypertensives, however, increase lateral prefrontal (Broca's area)/insula and amygdala/hippocampal rCBF more than normotensives. Initial results are sufficient to show that hypertension induces changes in rCBF. A tentative hypothesis is that a relatively general decrease in rCBF responsivity induces specific compensatory cognitive strategies as well as subcortical activation. The rCBF changes appear to have implications for information processing and, as such, hold promise for understanding prior reports relating hypertension to affective regulation and cardiovascular reactivity. Imaging techniques provide a powerful tool for psychosomatic research.

Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: a study using oxygen 15–labeled water PET

Background Myocardial perfusion single photon emission computed tomography (SPECT) occasionally fails to detect coronary stenosis in patients with coronary artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15–labeled water in areas with and without ischemia on technetium 99m tetrofosmin stress perfusion SPECT in patients with angiographically documented CAD. Methods and results Twenty-seven patients with CAD and eleven age-matched normal subjects were studied. Baseline myocardial blood flow (MBF) and MBF during hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg · kg −1 · min −1) were determined with the use of O-15–labeled water positron emission tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was performed for comparison. On the basis of the results of coronary angiography and SPECT, coronary segments were divided into 3 types: segments with coronary stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16), segments with coronary stenosis without a perfusion abnormality (group B, n = 42), and remote segments with no coronary stenosis or perfusion abnormality (group C, n = 18). Baseline MBF values were similar among the 3 groups. CFR in group A was lower (1.82 ± 0.54) than in group B (2.22 ± 0.87, P < .05), in group C (2.92 ± 1.21, P < .01), and in normal segments (3.86 ± 1.24, P < .001). CFR in group B was lower than in group C ( P < .02) and in normal segments ( P < .001). CFR in group C was lower than in normal segments ( P < .02). Conclusions Areas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas without a perfusion abnormality and with coronary stenosis, lowering of CFR was intermediate between the areas with a perfusion abnormality and remote segments. Moreover, CFR was slightly, but significantly, lower in remote segments in patients with CAD compared with normal segments.

Regional Cerebral Blood Flow Changes During Visually Induced Subjective Sadness in Healthy Elderly Persons

This study examined regional cerebral blood flow (rCBF) changes associated with visually induced sad affect in healthy elderly persons. Subjects viewed sadness-laden, happiness-laden, and emotionally neutral image sets while rCBF was recorded using [15O] water PET. The sad image set included human faces and scenery/objects (“scenes”). To control for secondary sensory processing, the neutral and happy comparison sets included exclusively either human faces or scenes. During the sad condition, the ventral prefrontal and temporal cortices were more active compared with happy and neutral scenes conditions and the thalamus was more active compared with happy and neutral faces conditions. Ventral prefrontal cortex and thalamus were associated with processing of sad visual stimuli, whether compared with neutral or happy stimuli. The specific findings associated with sad affect were contingent on the comparison stimuli content (scenes or human faces), not affect (i.e., comparison with neutral or happy conditions).