H2O Positron Emission Tomography Research Articles

Brain-Derived Neurotrophic Factor Val66Met Polymorphism Affects the Relationship Between an Anxiety-Related Personality Trait and Resting Regional Cerebral Blood Flow.

Brain-derived neurotrophic factor (BDNF) is an important modulator of constitutive stress responses mediated by limbic frontotemporal circuits, and its gene contains a functional polymorphism (Val66Met) that may influence trait stress sensitivity. Reports of an association of this polymorphism with anxiety-related personality traits have been controversial and without clear neurophysiological support. We, therefore, determined the relationship between resting regional cerebral blood flow (rCBF) and a well-validated measure of anxiety-related personality, the TPQ Harm Avoidance (HA) scale, as a function of BDNF Val66Met genotype. Sixty-four healthy participants of European ancestry underwent resting H215O positron emission tomography scans. For each genotype group separately, we first determined the relationship between participants' HA scores and their resting rCBF values in each voxel across the entire brain, and then directly compared these HA-rCBF relationships between Val66Met genotype groups. HA-rCBF relationships differed between Val homozygotes and Met carriers in several regions relevant to stress regulation: subgenual cingulate, orbital frontal cortex, and the hippocampal/parahippocampal region. In each of these areas, the relationship was positive in Val homozygotes and negative in Met carriers. These data demonstrate a coupling between trait anxiety and basal resting blood flow in frontolimbic neurocircuitry that may be determined in part by genetically mediated BDNF signaling.

Quantitative agreement between [(15)O]H2O PET and model free QUASAR MRI-derived cerebral blood flow and arterial blood volume.

The purpose of this study was to assess whether there was an agreement between quantitative cerebral blood flow (CBF) and arterial cerebral blood volume (CBVA) measurements by [(15)O]H2O positron emission tomography (PET) and model-free QUASAR MRI. Twelve healthy subjects were scanned within a week in separate MRI and PET imaging sessions, after which quantitative and qualitative agreement between both modalities was assessed for gray matter, white matter and whole brain region of interests (ROI). The correlation between CBF measurements obtained with both modalities was moderate to high (r(2): 0.28-0.60, P < 0.05), although QUASAR significantly underestimated CBF by 30% (P < 0.001). CBVA was moderately correlated (r(2): 0.28-0.43, P < 0.05), with QUASAR yielding values that were only 27% of the [(15)O]H2O-derived values (P < 0.001). Group-wise voxel statistics identified minor areas with significant contrast differences between [(15)O]H2O PET and QUASAR MRI, indicating similar qualitative CBVA and CBF information by both modalities. In conclusion, the results of this study demonstrate that QUASAR MRI and [(15)O]H2O PET provide similar CBF and CBVA information, but with systematic quantitative discrepancies.

Effects of erlotinib therapy on [(11)C]erlotinib uptake in EGFR mutated, advanced NSCLC.

BackgroundIn non-small cell lung cancer (NSCLC) patients off erlotinib therapy, positron emission tomography (PET) using [11C]erlotinib distinguished epidermal growth factor receptor (EGFR) mutations from wild-type EGFR. However, tumor uptake of [11C]erlotinib during erlotinib therapy is unknown. Therefore, the aims of this study were to evaluate tumor [11C]erlotinib uptake in NSCLC patients both on and off erlotinib therapy, to evaluate the effect of erlotinib therapy on tumor perfusion and its correlation to tumor [11C]erlotinib uptake, and also, to investigate simplified uptake parameters using arterial and venous blood samples.MethodsTen patients were to be scanned twice with a 1–2-week interval, i.e., on (E+) and off (E−) erlotinib therapy. Each procedure consisted of a low-dose CT scan, a 10-min dynamic [15O]H2O PET scan, and a 60-min dynamic [11C]erlotinib PET scan with arterial and venous sampling at six time points. In patients(E+), the optimal compartment model was analyzed using Akaike information criterion. In patients(E−), the uptake parameter was the volume of distribution (VT), estimated by using metabolite-corrected plasma input curves based on image-derived input functions and discrete arterial and venous blood samples. Tumor blood flow (TBF) was determined by rate constant of influx (K1) of [15O]H2O using the 1T2k model and correlated with VT and K1 values of [11C]erlotinib. The investigated simplified parameters were standardized uptake value (SUV) and tumor-to-blood ratio (TBR) at 40–60 min pi interval.ResultsOf the 13 patients included, ten were scanned twice. In patients(E+), [11C]erlotinib best fitted the 2T4k model with VT. In all patients, tumor VT(E+) was lower than VT(E−) (median VT(E−) = 1.61, range 0.77–3.01; median VT(E+) = 1.17, range 0.53–1.74; P = 0.004). Using [15O]H2O, five patients were scanned twice. TBF did not change with erlotinib therapy, TBF showed a positive trend towards correlation with [11C]erlotinib K1, but not with VT. TBR40–50 and TBR50–60, using both arterial and venous sampling, correlated with VT(E−) (all rs >0.9, P < 0.001), while SUV did not. In patients off and on therapy, venous TBR underestimated arterial TBR by 26 ± 12 and 9 ± 9 %, respectively.ConclusionsIn patients on erlotinib in therapeutic dose, tumor VT decreases with high variability, independent of tumor perfusion. For simplification of [11C]erlotinib PET scanning protocols, both arterial and venous TBR 40–60 min post injection can be used; however, arterial and venous TBR values should not be interchanged as venous values underestimate arterial values.Trial registrationRegistered at the Netherlands Trial Registry: NTR3670.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0169-8) contains supplementary material, which is available to authorized users.

Comparison of [(15)O] H2O Positron Emission Tomography and Functional Magnetic Resonance Imaging in Activation Studies.

[15O] H2O positron emission tomography (PET) has long been out of use in activation studies on the brain. Indeed, it is true that blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) has better spatial resolution and temporal resolution than PET, as well as no radiation exposure. However, PET and fMRI differ in their scope. Compared to fMRI, [15O] H2O PET offers advantages such as being quantifiable, less deteriorated by movement, and allowing for longitudinal studies. This article aimed to reassess the merits of PET in this context.

Abstract 10869: Role of Myocardial Perfusion, Sympathetic Denervation, and Scar Size in Predicting Inducibility of Ventricular Arrhythmia in Ischemic Cardiomyopathy

Introduction: Myocardial perfusion, scar size, sympathetic denervation and innervation-perfusion mismatch, obtained from positron emission tomography (PET) and late gadolinium enhanced cardiovascular magnetic resonance imaging (LGE-CMR), may all provide better risk prediction of ventricular arrhythmias (VA). There may, however, be overlap between these risk markers, as some are based on similar pathophysiology. The aim of this study was to assess the role of PET and LGE-CMR derived risk markers in predicting VA inducibility in the same patient population. Methods: Patients (n=52, 66 ± 9 years, 90% male, LVEF 29 ± 6%) with ischemic cardiomyopathy and left ventricular ejection fraction (LVEF) ≤35% who were referred for primary prevention implantable cardioverter-defibrillator (ICD) implantation were included. LGE-CMR was performed to assess LV volumes, function, and scar size. [ 15 O]H 2 O PET and [ 11 C]HED PET were performed to assess both resting and hyperemic myocardial blood flow (MBF), and sympathetic innervation. Perfusion and innervation defects, and mismatch were calculated. After ICD implantation, an electrophysiological study (EPS) was performed and was considered positive in case of sustained VA. Results: Patients with positive EPS (n=25) showed lower hyperemic MBF (1.36 ± 0.39 vs. 1.71 ± 0.39 mL·min -1 ·g -1 , P =0.003), larger innervation defect size (28 ± 12 vs. 21 ± 13%, P =0.048), and tended to have larger scar size (24 ± 13 vs. 18 ± 9 g, P =0.07) and perfusion defect size (22 ± 13 vs. 15 ± 11%, P =0.06) compared with EPS negative patients (n=27). No differences were observed in LV volumes, LVEF, and innervation-perfusion mismatch size. Multivariable analysis revealed that impaired hyperemic MBF was the only independent predictor for VA inducibility (OR 0.78, 95% CI 0.65-0.94, P =0.007). A combination of risk markers did not yield incremental predictive value over hyperemic MBF alone. Conclusion: Of all previously validated risk markers for VA, impaired hyperemic MBF was the only independent predictor of VA inducibility. Moreover, a combined approach of different imaging variables did not have incremental value. These results may suggest that quantitative PET perfusion imaging may be promising for risk prediction of VA.

Coronary vasomotor function in infarcted and remote myocardium after primary percutaneous coronary intervention

ObjectiveIn patients with acute myocardial infarction (AMI), coronary vasomotor function is impaired in the myocardial territory supplied by the culprit artery and in remote myocardium supplied by angiographically normal vessels....

Doppler-derived intracoronary physiology indices predict the occurrence of microvascular injury and microvascular perfusion deficits after angiographically successful primary percutaneous coronary intervention.

A total of 40% to 50% of patients with ST-segment-elevation myocardial infarction develop microvascular injury (MVI) despite angiographically successful primary percutaneous coronary intervention (PCI). We investigated whether hyperemic microvascular resistance (HMR) immediately after angiographically successful PCI predicts MVI at cardiovascular magnetic resonance and reduced myocardial blood flow at positron emission tomography (PET). Sixty patients with ST-segment-elevation myocardial infarction were included in this prospective study. Immediately after successful PCI, intracoronary pressure-flow measurements were performed and analyzed off-line to calculate HMR and indices derived from the pressure-velocity loops, including pressure at zero flow. Cardiovascular magnetic resonance and H2 (15)O PET imaging were performed 4 to 6 days after PCI. Using cardiovascular magnetic resonance, MVI was defined as a subendocardial recess of myocardium with low signal intensity within a gadolinium-enhanced area. Myocardial perfusion was quantified using H2 (15)O PET. Reference HMR values were obtained in 16 stable patients undergoing coronary angiography. Complete data sets were available in 48 patients of which 24 developed MVI. Adequate pressure-velocity loops were obtained in 29 patients. HMR in the culprit artery in patients with MVI was significantly higher than in patients without MVI (MVI, 3.33±1.50 mm Hg/cm per second versus no MVI, 2.41±1.26 mm Hg/cm per second; P=0.03). MVI was associated with higher pressure at zero flow (45.68±13.16 versus 32.01±14.98 mm Hg; P=0.015). Multivariable analysis showed HMR to independently predict MVI (P=0.04). The optimal cutoff value for HMR was 2.5 mm Hg/cm per second. High HMR was associated with decreased myocardial blood flow on PET (myocardial perfusion reserve <2.0, 3.18±1.42 mm Hg/cm per second versus myocardial perfusion reserve ≥2.0, 2.24±1.19 mm Hg/cm per second; P=0.04). Doppler-flow-derived physiological indices of coronary resistance (HMR) and extravascular compression (pressure at zero flow) obtained immediately after successful primary PCI predict MVI and decreased PET myocardial blood flow. http://www.trialregister.nl. Unique identifier: NTR3164.

Temporal plasticity involved in recovery from manual dexterity deficit after motor cortex lesion in macaque monkeys.

The question of how intensive motor training restores motor function after brain damage or stroke remains unresolved. Here we show that the ipsilesional ventral premotor cortex (PMv) and perilesional primary motor cortex (M1) of rhesus macaque monkeys are involved in the recovery of manual dexterity after a lesion of M1. A focal lesion of the hand digit area in M1 was made by means of ibotenic acid injection. This lesion initially caused flaccid paralysis in the contralateral hand but was followed by functional recovery of hand movements, including precision grip, during the course of daily postlesion motor training. Brain imaging of regional cerebral blood flow by means of H2 (15)O-positron emission tomography revealed enhanced activity of the PMv during the early postrecovery period and increased functional connectivity within M1 during the late postrecovery period. The causal role of these areas in motor recovery was confirmed by means of pharmacological inactivation by muscimol during the different recovery periods. These findings indicate that, in both the remaining primary motor and premotor cortical areas, time-dependent plastic changes in neural activity and connectivity are involved in functional recovery from the motor deficit caused by the M1 lesion. Therefore, it is likely that the PMv, an area distant from the core of the lesion, plays an important role during the early postrecovery period, whereas the perilesional M1 contributes to functional recovery especially during the late postrecovery period.

A network analysis of ¹⁵O-H₂O PET reveals deep brain stimulation effects on brain network of Parkinson's disease.

PurposeAs Parkinson's disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using cross-sectional positron emission tomography (PET) images in DBS studies.Materials and MethodsWe obtained [15O]H2O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects.ResultsICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum.ConclusionOur results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.

Abstract 18368: Evidence for Activation of Cerebral Autonomic Center in Response to Cardiac Electrical Stimulation in Humans -A New Finding of Cardio-Cerebral Connection

Introduction: Anterior cingulate cortex (ACC) is one of the cortical receptive fields of afferent nerves innervating the visceral organs and modulates autonomic nervous system in collaboration with hypothalamus and brainstem. Cardiac afferent nerves are associated with not only chest pain but also sympathetic arousal in heart failure, in which ACC could be involved. However, the cortical receptive fields of cardiac afferent nerves still remain to be elucidated. Hypothesis: We thus investigated whether ACC is activated in response to cardiac electrical stimulation in humans. Methods: We studied 10 patients (74.7±1.9 yrs, M/F 9/1) with cardiac pacemaker implantation. Before the measurement, mode of cardiac pacemaker was changed to VVI 80-90 bpm with 1.5V intensity. Cerebral blood flow (CBF) was measured using [15O]H2O positron emission tomography (PET) during sham stimulation (1.5V) and intense stimulation (7.5-8V). The CBF images of intense stimulation were compared with those of sham stimulation using SPM8, a common analysis tool for neuroimages. Cardiac sensation was evaluated with an ordinate scale after CBF measurements. Blood samples were obtained from the cubital vein before and after CBF measurements for plasma catecholamine levels (one patient was excluded for the analysis due to urination before the last blood sampling). Results: Intense stimulation did not induce cardiac sensation but significantly increased plasma adrenaline levels as compared with sham stimulation (intense, 6.1±1.8 vs. sham, 0.1±3.0 pg/ml, P=0.031, n=9 each). CBF in ACC was significantly increased in response to intense stimulation as compared with sham stimulation (intense, 64.6±0.7 vs. sham, 61.0±1.3 ml/100g/min, P=0.008, n=10 each) ( Figure, yellow arrowhead ). Conclusions: This study demonstrates for the first time that ACC could be the cortical receptive field of cardiac afferent nerves associated with sympathetic arousal in humans.

Abstract 19159: Assessment of Myocardial Viability After Acute Myocardial Infarction: A Head-to-head Comparison of the Perfusable Tissue Index by PET and Delayed Contrast-enhanced CMR

Introduction: Early recognition of viable myocardium is of great clinical importance after acute myocardial infarction (AMI). Delayed contrast-enhanced magnetic resonance imaging (DCE-CMR) has been validated extensively for the detection of viability. An alternative method for detecting viability is the perfusable tissue index (PTI), a positron emission tomography (PET) derived parameter, which is inversely related to the extent of myocardial scar (nonperfusable tissue). Aims: To investigate the predictive value of PTI on recovery of LV function after percutaneous coronary intervention (PCI) for AMI. Methods: Twenty-six patients with AMI successfully treated by PCI were included. Subjects were examined one week and three months after AMI with [15O]H2O PET and DCE-CMR to assess PTI, regional function and scar. Viability was defined as recovery of systolic wall thickening (SWT) ≥ 3.0 mm at follow-up. Results: A total of 396 segments were available for serial analysis. At baseline, 166 segments were dysfunctional, of which 125 (75%) exhibited significant DCE and were located in the myocardial territory supplied by the culprit-artery. Fourty-nine of these dysfunctional segments showed full recovery during follow-up (viable), whereas 76 segments remained dysfunctional (nonviable). Baseline PTI of viable segments was 0.94 ± 0.07 and was significantly higher compared to nonviable segments (0.80 ± 0.11, p = 0.01). The optimal cut-off value for the PTI was 0.85 with a sensitivity of 92% and specificity of 71%, and an area under the curve (AUC) of 0.88. In comparison, a cut-off value of 40% for the extent of DCE resulted in a sensitivity of 75% and a specificity of 65%, and an AUC of 0.75 (p = 0.02 vs PTI). Conclusions: This study shows that assessment of myocardial viability shortly after reperfused AMI is feasible with PET, and that the PTI is a good prognostic indicator for recovery of contractile function when compared to DCE-CMR.

Quantitative Assessment of Myocardial Perfusion in the Detection of Significant Coronary Artery Disease: Cutoff Values and Diagnostic Accuracy of Quantitative [15O]H2O PET Imaging

BackgroundRecent studies have demonstrated improved diagnostic accuracy for detecting coronary artery disease (CAD) when myocardial blood flow (MBF) is quantified in absolute terms, but there are no uniformly accepted cutoff values for hemodynamically significant CAD. ObjectivesThe goal of this study was to determine cutoff values for absolute MBF and to evaluate the diagnostic accuracy of quantitative [15O]H2O positron emission tomography (PET). MethodsA total of 330 patients underwent both quantitative [15O]H2O PET imaging and invasive coronary angiography in conjunction with fractional flow reserve measurements. A stenosis >90% and/or fractional flow reserve ≤0.80 was considered obstructive; a stenosis <30% and/or fractional flow reserve >0.80 was nonobstructive. ResultsHemodynamically significant CAD was diagnosed in 116 (41%) of 281 patients who fulfilled study criteria for CAD. Resting perfusion was 1.00 ± 0.25 and 0.92 ± 0.23 ml/min/g in regions supplied by nonstenotic and significantly stenosed vessels, respectively (p < 0.001). During stress, perfusion increased to 3.26 ± 1.04 ml/min/g and 1.73 ± 0.67 ml/min/g, respectively (p < 0.001). The optimal cutoff values were 2.3 and 2.5 for hyperemic MBF and myocardial flow reserve, respectively. For MBF, these cutoff values showed a sensitivity, specificity, and accuracy for detecting significant CAD of 89%, 84%, and 86%, respectively, at a per-patient level and 87%, 85%, and 85% at a per-vessel level. The corresponding myocardial flow reserve values were 86%, 72%, and 78% (per patient) and 80%, 82%, and 81% (per vessel). Age and sex significantly affected diagnostic accuracy of quantitative PET. ConclusionsQuantitative MBF measurements with the use of [15O]H2O PET provided high diagnostic performance, but both sex and age should be taken into account.

TCT-290 Assessment Of Myocardial Viability After Acute Myocardial Infarction: A Head-To-Head Comparison Of The Perfusable Tissue Index By PET And Delayed Contrast-Enhanced CMR

Introduction: Early recognition of viable myocardium is of great clinical importance after acute myocardial infarction (AMI). Delayed contrast-enhanced magnetic resonance imaging (DCE-CMR) has been validated extensively for the detection of viability. An alternative method for detecting viability is the perfusable tissue index (PTI), a positron emission tomography (PET) derived parameter, which is inversely related to the extent of myocardial scar (nonperfusable tissue). Aims: To investigate the predictive value of PTI on recovery of LV function after percutaneous coronary intervention (PCI) for AMI. Methods: Twenty-six patients with AMI successfully treated by PCI were included. Subjects were examined one week and three months after AMI with [15O]H2O PET and DCE-CMR to assess PTI, regional function and scar. Viability was defined as recovery of systolic wall thickening (SWT) ≥ 3.0 mm at follow-up. Results: A total of 396 segments were available for serial analysis. At baseline, 166 segments were dysfunct...

Transient Antiangiogenic Treatment Improves Delivery of Cytotoxic Compounds and Therapeutic Outcome in Lung Cancer

Extensive oncologic experience argues that the most efficacious applications of antiangiogenic agents rely upon a combination with cytotoxic drugs. Yet there remains a lack of clarity about how to optimize scheduling for such drug combinations. Prudent antiangiogenic therapy might transiently normalize blood vessels to improve tumor oxygenation and drug exposure. Using [(15)O]H2O positron emission tomography imaging in a preclinical mouse model of non-small cell lung cancer, we observed that short-term treatment with the vascular endothelial growth factor receptor/platelet-derived growth factor receptor inhibitor PTK787 licensed a transient window of improved tumor blood flow. The improvement observed was associated with a reduced leakiness from tumor vessels, consistent with induction of a vascular normalization process. Initiation of a cytotoxic treatment in this window of tumor vessel normalization resulted in increased efficacy, as illustrated by improved outcomes of erlotinib administration after initial PTK787 treatment. Notably, intermittent PTK787 treatment also facilitated long-term tumor regression. In summary, our findings offer strong evidence that short-term antiangiogenic therapy can promote a transient vessel normalization process that improves the delivery and efficacy of a targeted cytotoxic drug.

Impact of anatomical and functional severity of coronary atherosclerotic plaques on the transmural perfusion gradient: a [15O]H2O PET study

Myocardial ischaemia occurs principally in the subendocardial layer, whereas conventional myocardial perfusion imaging provides no information on the transmural myocardial blood flow (MBF) distribution. Subendocardial perfusion measurements and quantification of the transmural perfusion gradient (TPG) could be more sensitive and specific for the detection of coronary artery disease (CAD). The current study aimed to determine the impact of lesion severity as assessed by the fractional flow reserve (FFR) on subendocardial perfusion and the TPG using [(15)O]H2O positron emission tomography (PET) imaging in patients evaluated for CAD. Sixty-six patients with anginal chest pain were prospectively enrolled and underwent [(15)O]H2O myocardial perfusion PET imaging. Subsequently, invasive coronary angiography was performed and FFR obtained in all coronary arteries irrespective of the PET imaging results. Thirty (45%) patients were diagnosed with significant CAD (i.e. FFR ≤0.80), whereas on a per vessel analysis (n = 198), 53 (27%) displayed a positive FFR. Transmural hyperaemic MBF decreased significantly from 3.09 ± 1.16 to 1.67 ± 0.57 mL min(-1) g(-1) (P < 0.001) in non-ischaemic and ischaemic myocardium, respectively. The TPG decreased during hyperaemia when compared with baseline (1.20 ± 0.14 vs. 0.94 ± 0.17, P < 0.001), and was lower in arteries with a positive FFR (0.97 ± 0.16 vs. 0.88 ± 0.18, P < 0.01). A TPG threshold of 0.94 yielded an accuracy to detect CAD of 59%, which was inferior to transmural MBF with an optimal cutoff of 2.20 mL min(-1) g(-1) and an accuracy of 85% (P < 0.001). Diagnostic accuracy of subendocardial perfusion measurements was comparable with transmural MBF (83 vs. 85%, respectively, P = NS). Cardiac [(15)O]H2O PET imaging is able to distinguish subendocardial from subepicardial perfusion in the myocardium of normal dimensions. Hyperaemic TPG is significantly lower in ischaemic myocardium. This technique can potentially be employed to study subendocardial perfusion impairment in more detail. However, the diagnostic accuracy of subendocardial hyperaemic perfusion and TPG appears to be limited compared with quantitative transmural MBF, warranting further study.

The effects of catecholamine depletion on the neural response to fearful faces in remitted depression.

Recent evidence suggests that increased psychophysiological response to negatively valenced emotional stimuli found in major depressive disorder (MDD) may be associated with reduced catecholaminergic neurotransmission. Fourteen unmedicated, remitted subjects with MDD (RMDD) and 13 healthy control subjects underwent catecholamine depletion with oral α-methyl-para-tyrosine (AMPT) in a randomized, placebo-controlled, double-blind crossover trial. Subjects were exposed to fearful (FF) and neutral faces (NF) during a scan with [15O]H2O positron emission tomography to assess the brain-catecholamine interaction in brain regions previously associated with emotional face processing. Treatment with AMPT resulted in significantly increased, normalized cerebral blood flow (CBF) in the left inferior temporal gyrus (ITG) and significantly decreased CBF in the right cerebellum across conditions and groups. In RMDD, flow in the left posterior cingulate cortex (PCC) increased significantly in the FF compared to the NF condition after AMPT, but remained unchanged after placebo, whereas healthy controls showed a significant increase under placebo and a significant decrease under AMPT in this brain region. In the left dorsolateral prefrontal cortex (DLPFC), flow decreased significantly in the FF compared to the NF condition under AMPT, and increased significantly under placebo in RMDD, whereas healthy controls showed no significant differences. Differences between AMPT and placebo of within-session changes in worry-symptoms were positively correlated with the corresponding changes in CBF in the right subgenual prefrontal cortex in RMDD. In conclusion, this study provided evidence for a catecholamine-related modulation of the neural responses to FF expressions in the left PCC and the left DLPFC in subjects with RMDD that might constitute a persistent, trait-like abnormality in MDD.

Kinetic modeling in the context of cerebral blood flow quantification by H215O positron emission tomography: The meaning of the permeability coefficient in Renkin–Crone׳s model revisited at capillary scale

One the one hand, capillary permeability to water is a well-defined concept in microvascular physiology, and linearly relates the net convective or diffusive mass fluxes (by unit area) to the differences in pressure or concentration, respectively, that drive them through the vessel wall. On the other hand, the permeability coefficient is a central parameter introduced when modeling diffusible tracers transfer from blood vessels to tissue in the framework of compartmental models, in such a way that it is implicitly considered as being identical to the capillary permeability. Despite their simplifying assumptions, such models are at the basis of blood flow quantification by H215O Positron Emission Tomgraphy.In the present paper, we use fluid dynamic modeling to compute the transfers of H215O between the blood and brain parenchyma at capillary scale. The analysis of the so-obtained kinetic data by the Renkin–Crone model, the archetypal compartmental model, demonstrates that, in this framework, the permeability coefficient is highly dependent on both flow rate and capillary radius, contrarily to the central hypothesis of the model which states that it is a physiological constant. Thus, the permeability coefficient in Renkin–Crone׳s model is not conceptually identical to the physiologic permeability as implicitly stated in the model. If a permeability coefficient is nevertheless arbitrarily chosen in the computed range, the flow rate determined by the Renkin–Crone model can take highly inaccurate quantitative values.The reasons for this failure of compartmental approaches in the framework of brain blood flow quantification are discussed, highlighting the need for a novel approach enabling to fully exploit the wealth of information available from PET data.

Accuracy and precision of pseudo-continuous arterial spin labeling perfusion during baseline and hypercapnia: A head-to-head comparison with 15O H2O positron emission tomography

Measurements of the cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) provide useful information about cerebrovascular condition and regional metabolism. Pseudo-continuous arterial spin labeling (pCASL) is a promising non-invasive MRI technique to quantitatively measure the CBF, whereas additional hypercapnic pCASL measurements are currently showing great promise to quantitatively assess the CVR. However, the introduction of pCASL at a larger scale awaits further evaluation of the exact accuracy and precision compared to the gold standard. 15O H2O positron emission tomography (PET) is currently regarded as the most accurate and precise method to quantitatively measure both CBF and CVR, though it is one of the more invasive methods as well. In this study we therefore assessed the accuracy and precision of quantitative pCASL-based CBF and CVR measurements by performing a head-to-head comparison with 15O H2O PET, based on quantitative CBF measurements during baseline and hypercapnia. We demonstrate that pCASL CBF imaging is accurate during both baseline and hypercapnia with respect to 15O H2O PET with a comparable precision. These results pave the way for quantitative usage of pCASL MRI in both clinical and research settings.

Resting brain activity varies with dream recall frequency between subjects.

Dreaming is still poorly understood. Notably, its cerebral underpinning remains unclear. Neuropsychological studies have shown that lesions in the temporoparietal junction (TPJ) and/or the white matter of the medial prefrontal cortex (MPFC) lead to the global cessation of dream reports, suggesting that these regions of the default mode network have key roles in the dreaming process (forebrain 'dream-on' hypothesis). To test this hypothesis, we measured regional cerebral blood flow (rCBF) using [(15)O]H2O positron emission tomography in healthy subjects with high and low dream recall frequencies (DRFs) during wakefulness (rest) and sleep (rapid eye movement (REM) sleep, N2, and N3). Compared with Low recallers (0.5 ± 0.3 dream recall per week in average), High recallers (5.2 ± 1.4) showed higher rCBF in the TPJ during REM sleep, N3, and wakefulness, and in the MPFC during REM sleep and wakefulness. We demonstrate that the resting states of High recallers and Low recallers differ during sleep and wakefulness. It coheres with previous ERP results and confirms that a high/low DRF is associated with a specific functional organization of the brain. These results support the forebrain 'dream-on' hypothesis and suggest that TPJ and MPFC are not only involved in dream recall during wakefulness but also have a role in dreaming during sleep (production and/or encoding). Increased activity in the TPJ and MPFC might promote the mental imagery and/or memory encoding of dreams. Notably, increased activity in TPJ might facilitate attention orienting toward external stimuli and promote intrasleep wakefulness, facilitating the encoding of the dreams in memory.

Impaired Hyperemic Myocardial Blood Flow Is Associated With Inducibility of Ventricular Arrhythmia in Ischemic Cardiomyopathy

Risk stratification for ventricular arrhythmias (VAs) is important to refine selection criteria for primary prevention implantable cardioverter defibrillator therapy. Impaired hyperemic myocardial blood flow (MBF) is associated with increased mortality rate in ischemic and nonischemic cardiomyopathy, which may be attributed to electric instability inducing VAs. The aim of this pilot study was to assess whether hyperemic MBF impairment may be related with VA inducibility in patients with ischemic cardiomyopathy. Thirty patients with ischemic cardiomyopathy referred for primary prevention implantable cardioverter defibrillator implantation were prospectively included (26 men; 65±8 years old; left ventricular ejection fraction, 29±6%). [15O]H2O positron-emission tomography was performed to quantify resting MBF, hyperemic MBF, and coronary flow reserve. Left ventricular dimensions, function, and scar burden were assessed with cardiovascular magnetic resonance imaging. An electrophysiological study was performed to test VA inducibility. Positive electrophysiological study patients (n=12) showed reduced hyperemic MBF (1.25±0.30 versus 1.66±0.38 mL·min(-1)·g(-1); P<0.01) and coronary flow reserve (1.59±0.49 versus 2.12±0.48; P<0.01) compared with electrophysiological study negative patients (n=18). In electrophysiological study positive patients, the number of scar segments>75% transmurality was higher (P<0.05), although scar size and border zone did not differ. Receiver-operating characteristic curve analysis indicated that impaired hyperemic MBF (area under the curve, 0.84; 95% confidence intervals [0.69-0.99]) and coronary flow reserve (area under the curve, 0.77; 95% confidence intervals [0.57-0.96]) were associated with VA inducibility. In this pilot study, impaired hyperemic MBF and coronary flow reserve were associated with VA inducibility in patients with ischemic cardiomyopathy. These results are hypothesis generating for a potential role of quantitative positron-emission tomography perfusion imaging in risk stratification for VAs.