Regional cerebral blood flow (rCBF) is spatially and temporally adjusted to local energy needs. This coupling involves dilation of vessels both at the site of metabolite exchange and upstream of the activated region. Deficits in upstream blood supply limit the 'capacity to raise rCBF' in response to functional activation and therefore compromise brain function. We here demonstrate in rats that the 'capacity to raise rCBF' can be determined from real-time measurements of rCBF using laser speckle imaging during an energy challenge induced by cortical spreading depolarizations (CSDs). Cortical spreading depolarizations (CSDs) occur with high incidence in stroke and various other brain injuries and cause large metabolic changes. Various conditions of cerebral perfusion were induced, either by modifying microvascular tone, or by altering upstream blood supply independently. The increase in rCBF per unit of time in response to CSD was linearly correlated to the upstream blood supply. In an experimental model of stroke, we found that this marker of the capacity to raise rCBF which, in pathologic tissue may be additionally limited by impaired vasoactive signaling, was a better indicator of the functional status of cerebral tissue than local rCBF levels.

Obstructive sleep apnea (OSA) is a condition characterized by upper airway muscle atonia with continued diaphragmatic efforts, resulting in repeated airway obstructions, periods of intermittent hypoxia, large thoracic pressure changes, and substantial shifts in arterial pressure with breathing cessation and resumption. The hypoxic exposure and hemodynamic changes likely induce the structural and functional deficits found in multiple brain areas, as shown by magnetic resonance imaging (MRI) procedures. Altered cerebral blood flow (CBF) may contribute to these localized deficits; thus, we examined regional CBF, using arterial spin labeling procedures, in 11 OSA (age, 49.1±12.2 years; 7 male) and 16 control subjects (42.3±10.2 years; 6 male) with a 3.0-Tesla MRI scanner. CBF maps were calculated, normalized to a common space, and regional CBF values across the brain quantified. Lowered CBF values emerged near multiple bilateral brain sites in OSA, including the corticospinal tracts, superior cerebellar peduncles, and pontocerebellar fibers. Lateralized, decreased CBF appeared near the left inferior cerebellar peduncles, left tapetum, left dorsal fornix/stria terminalis, right medial lemniscus, right red nucleus, right midbrain, and midline pons. Regional CBF values in OSA are significantly reduced in major sensory and motor fiber systems and motor regulatory sites, especially in structures mediating motor coordination; those reductions are often lateralized. The asymmetric CBF declines in motor regulatory areas may contribute to loss of coordination between upper airway and diaphragmatic musculature, and lead to further damage in the syndrome.

There is increasing evidence of central hyperexcitability in chronic whiplash-associated disorders (cWAD). However, little is known about how an apparently simple cervical spine injury can induce changes in cerebral processes. The present study was designed (1) to validate previous results showing alterations of regional cerebral blood flow (rCBF) in cWAD, (2) to test if central hyperexcitability reflects changes in rCBF upon non-painful stimulation of the neck, and (3) to verify our hypothesis that the missing link in understanding the underlying pathophysiology could be the close interaction between the neck and midbrain structures. For this purpose, alterations of rCBF were explored in a case-control study using H2(15)O positron emission tomography, where each group was exposed to four different conditions, including rest and different levels of non-painful electrical stimulation of the neck. rCBF was found to be elevated in patients with cWAD in the posterior cingulate and precuneus, and decreased in the superior temporal, parahippocampal, and inferior frontal gyri, the thalamus and the insular cortex when compared with rCBF in healthy controls. No differences in rCBF were observed between different levels of electrical stimulation. The alterations in regions directly involved with pain perception and interoceptive processing indicate that cWAD symptoms might be the consequence of a mismatch during the integration of information in brain regions involved in pain processing.

An increasing number of studies have demonstrated that disease states of the endocrine or exocrine pancreas aggravate one another, which implies bidirectional blood flow between islets and exocrine cells. However, this is inconsistent with the current model of unidirectional blood flow, which is strictly from islets to exocrine tissues. This conventional model was first proposed in 1932, and it has never to our knowledge been revisited to date. Here, large-scale image capture was used to examine the spatial relationship between islets and blood vessels in the following species: human, monkey, pig, rabbit, ferret, and mouse. While some arterioles passed by or traveled through islets, the majority of islets had no association with them. Islets with direct contact with the arteriole were significantly larger in size and fewer in number than those without contact. Unique to the pancreas, capillaries directly branched out from the arterioles and have been labeled as "small arterioles" in past studies. Overall, the arterioles emerged to feed the pancreas regionally, not specifically targeting individual islets. Vascularizing the pancreas in this way may allow an entire downstream region of islets and acinar cells to be simultaneously exposed to changes in the blood levels of glucose, hormones, and other circulating factors.

In vivo determination of regional pulmonary blood flow (PBF) is a valuable tool for the evaluation of many lung diseases. In this study, the use of 68Ga-DOTA PET for the in vivo quantitative determination of regional PBF is proposed. This methodology was implemented and tested in healthy pigs and validated using fluorescent microspheres. The study was performed on young large white pigs (n = 4). To assess the reproducibility and consistency of the method, three PET scans were obtained for each animal. Each radiotracer injection was performed simultaneously to the injection of fluorescent microspheres. PBF images were generated applying a two-compartment exchange model over the dynamic PET images. PET and microspheres values were compared by regression analysis and Bland-Altman plot.

Objective: Clinical and radiological findings on neurosyphilis are fairly non-specific and there is a paucity of functional neuroimaging studies on neurosyphilis other than case reports and case series. The purpose of this study was to investigate brain perfusion abnormalities in patients with neurosyphilis. Methods: Four HIV-negative neurosyphilis patients and 4 healthy controls underwent clinical evaluation, brain technetium-99m ethyl cysteinate dimer (99mTc-ECD) single-photon emission computed tomography (SPECT) imaging, and neuropsychological assessments which included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Clinical Dementia Rating-Sum of Boxes (CDR-SOB), and Global Deterioration Scale (GDS). Voxel-wise differences in regional cerebral blood flow were compared between the two groups. Results: Neuropsychological test results indicated cognitive impairment in all patients. SPECT analysis revealed multifocal hypoperfusion predominantly in the frontal, insular, and posterior cingulate regions in neurosyphilis patients compared with healthy controls (family-wise error corrected p < 0.05). Conclusions: Together with previous findings, our results suggest that the hypoperfusion in the frontal, insular, and posterior cingulate regions may reflect cognitive impairments observed in neurosyphilis patients. Further studies with larger samples are needed to confirm our findings.

Aberrant motor behaviour (AMB) in Alzheimer's disease shares behavioural correlates with obsessive compulsive disorder (OCD). We investigated whether AMB was also comparable in terms of metabolic activity in the orbitofrontal cortex (OFC), an area shown to be hyperactive in OCD. In this study 135 patients meeting research criteria for Alzheimer's disease were identified from a database of patients recruited as part of a phase II drug trial. These patients were assessed using the Neuropsychiatric Inventory, the Alzheimer's disease assessment scale, cognitive subscale and perfusion SPECT performed with 99Tc(m) hexamethylpropyleneamine oxime. Regions of interest were created for orbitofrontal cortices and basal ganglia. In 35 patients with AMB, adjusted tracer uptake was greater in the OFC. This reached statistical significance in right superior, left superior, right medial and left medial orbital gyri (p < 0.05). The association between AMB and hyperactivity in the OFC remained significant after adjusting for the presence of anxiety. These results parallel the OFC hypermetabolism consistently seen in OCD. One model of OCD, proposes that dysfunctional interactions between frontal regions, including the OFC, produce the characteristic symptoms of OCD. The behaviour is though to be brought about by a perceived incompleteness of performing a task and is caused by an error in normal reward signals initiated upon task completion. These finding indicate that AMB in Alzheimer's disease are brought about by the same mechanistic failure.

Tc99 HMPAO SPECT and T1 weighted 3D MRI scans were acquired in cognitively intact subjects with Parkinson's disease (PD) (n = 31), and in PD subjects with dementia (PDD) (n = 34), healthy controls (n = 37), those with Alzheimer's disease (AD) (n = 32), and those with dementia with Lewy bodies (DLB) (n = 15). We used SPM99 to look for regions which showed a reduction in perfusion on SPECT not related to associated structural brain changes assessed by a MRI scan. The precuneus and inferior lateral parietal regions showed a perfusion deficit in Parkinson's disease with dementia, similar to the pattern observed in DLB. In comparison, AD showed a perfusion deficit in the midline parietal region, in a more anterior and inferior location than in PDD, involving the posterior cingulate as well as the precuneus. The perfusion deficits in PDD are similar those in DLB, and in a location associated with visual processing, and may be associated with the visuospatial perception deficits which are present in persons with DLB and PDD.

Positron tomography was used to investigate modulations of brain activity during the so-called resting state that may occur due to a concurrent cognitive training. Twelve subjects were repeatedly scanned during resting periods and while solving logical problems containing a bias causing them to make reasoning errors. At experiment mid-time, eight subjects were trained to inhibit the reasoning bias so that their performance in solving logical problems dramatically increased afterwards, while the other four subjects were trained to logical reasoning only which did not help improving their performance. In the subgroup of subjects who increased their performance after training, we found that during the post-training resting periods, as compared to pre-training resting periods, brain activity increases in areas not belonging to the classical resting network, namely the midbrain, thalamus, peristriate, inferior frontal, and ventromedial prefrontal cortices. Strikingly, in this subgroup of subjects, these same areas were found to be also more active during post-training successful execution of the logical task, as compared to pre-training erroneous execution of the task. Such findings were not observed in the subgroup of subjects who did not improve their performance after training to logic only. These results indicate that the brain default mode is a dynamic state during which context dependent local increases of cerebral blood flow may occur on a short-term, likely for the consolidation of newly acquired knowledge.

The posterior hippocampus (pHp) plays a major role in the processing and storage of drug-related cues and is linked to striatal-limbic brain circuits involved with craving and drug salience. We have recently reported that increased basal regional cerebral blood flow (rCBF) in a pHp loci, as measured by pseudo-continuous arterial spin labeling magnetic resonance imaging, predicted days to cocaine relapse following residential treatment. In this secondary analysis, we explored whether rCBF in this same pHp region would successfully predict 30-day point prevalence abstinence 60 days following residential treatment in an independent group of previously studied participants with cocaine dependence. rCBF was assessed with single photon emission computerized tomography during a saline infusion in 21 cocaine dependence and 22 healthy control participants. pHp rCBF was significantly higher in those endorsing substance use (n = 10) relative to both abstinent (n = 11) (p < 0.001) and control (p < 0.05) participants. There were no significant differences in measured demographic or clinical variables between the actively using and non-using participants. This replicative finding suggests that heightened pHp activation is a significant predictor of substance use in cocaine-dependent individuals, possibly reflecting a neural susceptibility to continued drug cues.

Prior studies have demonstrated decreasing cerebral blood flow (CBF) in normal aging, but the full spatial pattern and potential mechanism of changes in CBF remain to be elucidated. Specifically, existing data have not been entirely consistent regarding the spatial distribution of such changes, potentially a result of neglecting the effect of age-related tissue atrophy in CBF measurements. In this work, we use pulsed arterial-spin labelling to quantify regional CBF in 86 cognitively and physically healthy adults, aged 23 to 88 years. Surface-based analyses were utilized to map regional decline in CBF and cortical thickness with advancing age, and to examine the spatial associations and dissociations between these metrics. Our results demonstrate regionally selective age-related reductions in cortical perfusion, involving the superior-frontal, orbito-frontal, superior-parietal, middle-inferior temporal, insular, precuneus, supramarginal, lateral-occipital and cingulate regions, while subcortical CBF was relatively preserved in aging. Regional effects of age on CBF differed from that of grey-matter atrophy. In addition, the pattern of CBF associations with age displays an interesting similarity with the default-mode network. These findings demonstrate the dissociation between regional CBF and structural alterations specific to normal aging, and augment our understanding of mechanisms of pathology in older adults.

Cervical dystonia is considered as a network disorder affecting various brain regions in recent days. Presumably, deep brain stimulation (DBS) of the internal segment of globus pallidus (GPi) may exert therapeutic effects for cervical dystonia through modulation of the aberrant brain networks. In the present study, we investigated postoperative regional cerebral blood flow (rCBF) changes after GPi DBS using single-photon emission computed tomography (SPECT) to identify significant activity changes in several relevant brain areas of cervical dystonia patients.

Perfusion MRI is an important modality in many brain imaging protocols, since it probes cerebrovascular changes in aging and many diseases; however, it may not be always available.

Systemic blood flow in patients on extracorporeal assist devices is frequently not or only minimally pulsatile. Loss of pulsatile brain perfusion, however, has been implicated in neurological complications. Furthermore, the adverse effects of absent pulsatility on the cerebral microcirculation are modulated similarly as CO2 vasoreactivity in resistance vessels. During support with an extracorporeal assist device swings in arterial carbon dioxide partial pressures (PaCO2) that determine cerebral oxygen delivery are not uncommon-especially when CO2 is eliminated by the respirator as well as via the gas exchanger of an extracorporeal membrane oxygenation machine. We, therefore, investigated whether non-pulsatile flow affects cerebrovascular CO2 reactivity (CVR) and regional brain oxygenation (rSO2).

Neuroimaging of opiate-dependent individuals indicates both altered brain structure and function. Magnetic resonance-based arterial spin labeling has been used to measure noninvasively cerebral blood flow (i.e. perfusion) in alcohol, tobacco and stimulant dependence; only one arterial spin labeling paper in opiate-dependent individuals demonstrated frontal and parietal perfusion deficits. Additional research on regional brain perfusion in opiate dependence and its relationship to cognition and self-regulation (impulsivity, risk taking and decision making) may inform treatment approaches for opiate-dependent individuals. Continuous arterial spin labeling magnetic resonance imaging at 4 T and neuropsychological measures assessed absolute brain perfusion levels, cognition and self-regulation in 18 cigarette smoking opiate-dependent individuals (sODI) stable on buprenorphine maintenance therapy. The sODI were compared with 20 abstinent smoking alcohol-dependent individuals (a substance-dependent control group), 35 smoking controls and 29 nonsmoking controls. sODI had lower perfusion in several cortical and subcortical regions including regions within the brain reward/executive oversight system compared with smoking alcohol-dependent individuals and nonsmoking controls. Perfusion was increased in anterior cingulate cortex and globus pallidus of sODI. Compared with all other groups, sODI had greater age-related declines in perfusion in most brain reward/executive oversight system and some other regions. In sODI, lower regional perfusion related to greater substance use, higher impulsivity and weaker visuospatial skills. Overall, sODI showed cortical and subcortical hypoperfusion and hyperperfusion. Relating to neuropsychological performance and substance use quantities, the frontal perfusion alterations are clinically relevant and constitute potential targets for pharmacological and cognitive-based therapeutic interventions to improve treatment outcome in opiate dependence.

Autistic spectrum traits are postulated to lie on a continuum that extends between individuals with autism and individuals with typical development. The present study was carried out to investigate functional and network abnormalities associated with autistic spectrum trait in healthy male subjects.

The dose-dependent effect of isoflurane on regional CBF of cortical and subcortical structures in anesthetized macaque monkeys was investigated with the Continuous ASL MRI technique. High concentration of isoflurane resulted in global CBF increase and blood pressure decrease. Evident CBF change was observed in the subcortical structures. Specifically, CBF in thalamus and cerebellum was increased about 39% and 55% when isoflurane concentration was changed from 0.75% to 1.5%, respectively. Also, those regional CBF changes correlated linearly with isoflurane inspiratory concentrations, indicating impaired CBF autoregulation in these structures. In contrast, no obvious CBF changes were observed in anterior cingulated cortex, motor cortex, medial prefrontal cortex, and caudate. The results demonstrate that, under the 0.75-1.5% isoflurane maintenance doses, the CBF auto-regulation is well preserved in the cerebral cortical regions and caudate, but impaired in thalamus and cerebellum, indicating disturbed CBF-metabolism coupling and functional response in specific subcortical regions of anesthetized macaque monkeys.

The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-stimulated insulin secretion, and affects β-cell turnover. This study aimed at evaluating if some of the beneficial effects of GIP on glucose homeostasis can be explained by modulation of islet blood flow. Anesthetized Sprague-Dawley rats were infused intravenously with different doses of GIP (10, 20, or 60 ng/kg*min) for 30 min. Subsequent organ blood flow measurements were performed with microspheres. In separate animals, islets were perfused ex vivo with GIP (10-6 -10-12  mol/L) during normo- and hyperglycemia and arteriolar responsiveness was recorded. The highest dose of GIP potentiated insulin secretion during hyperglycemia, but had no effect in normoglycemic rats. The highest GIP concentration decreased blood perfusion of whole pancreas, pancreatic islets, duodenum, colon, liver and kidneys. The decrease in blood flow was unaffected by ganglion blockade or adenosine receptor inhibition. In contrast to this, in single perfused islets GIP induced a dose-dependent arteriolar dilation. Thus, high doses of GIP exert a direct dilatory effect on islet arterioles in isolated islets, but induce a generalized vasoconstriction in splanchnic organs, including the whole pancreas and islets, in vivo. The latter effect is unlikely to be mediated by adenosine, the autonomic nervous system, or endothelial mediators.

Regional cerebral blood flow (CBF) has a complex relationship with cognitive functioning such that cognitively unimpaired individuals at risk for Alzheimer's disease (AD) may show regional hyperperfusion, while those with cognitive impairment typically show hypoperfusion. Diabetes and word-list intrusion errors are both linked to greater risk of cognitive decline and dementia. Our study examined associations between fasting blood glucose, word-list intrusion errors, and regional CBF. 113 cognitively unimpaired older adults had arterial spin labeling MRI to measure CBF in a priori AD vulnerable regions: medial temporal lobe (MTL), inferior parietal lobe (IPL), precuneus, medial orbitofrontal cortex (mOFC), and pericalcarine (control region). Hierarchical linear regressions, adjusting for demographics, vascular risk, and reference CBF region, examined the main effect of blood glucose on regional CBF as well as whether intrusions moderated this relationship. Higher glucose was associated with higher CBF in the precuneus (β = .134, 95% CI = .007 to .261, p = .039), IPL (β = .173, 95% CI = .072 to .276, p = .001), and mOFC (β = .182, 95% CI = .047 to .320, p = .009). There was no main effect of intrusions on CBF across regions. However, the glucose x intrusions interaction was significant such that having higher glucose levels and more intrusion errors was associated with reduced CBF in the MTL (β = -.186, 95% CI = -.334 to -.040, p = .013) and precuneus (β = -.146, 95% CI = -.273 to -.022, p = .022). These findings may reflect early neurovascular dysregulation, whereby higher CBF is needed to maintain unimpaired cognition in individuals with higher glucose levels. However, lower regional CBF in unimpaired participants with both higher glucose and more intrusions suggests a failure in this early compensatory mechanism that may signal a decrease in neural activity in AD vulnerable regions.

The present study investigated the role of the postinjection interval in determining the functional consequences of acute ethanol administration in the CNS. Regional cerebral blood flow (RCBF) was determined by the [14C]iodoantipyrine method in 33 brain structures of ethanol-naive Sprague-Dawley rats. In the first experiment, changes in RCBF were assessed 5 and 15 min after a 0.8 g/kg (i.p.) dose of ethanol or water. Five minutes after treatment, rates of RCBF were increased in the motor cortex, agranular insular cortex, and the olfactory tubercle compared to water controls. No significant differences compared to control were found at the 15-min time point, despite the continued presence of ethanol in the blood. Experiment 2 tested whether blood ethanol level was the sole determinant of this response to ethanol by comparing animals with the same blood ethanol level at the 5- and 15-min time points. Greater rates of RCBF were found at 5 min postinjection compared to 15 min, in the motor cortex, agranular insular cortex, caudate/putamen, cerebellum, and the lateral septum. These data demonstrate that the rates of cerebral blood flow are increased in regionally discrete portions of the rat brain shortly after ethanol administration. Furthermore, blood ethanol level is not the exclusive factor governing this functional response.