Absolute Cerebral Blood Flow Research Articles

All-optics technique for monitoring absolute cerebral blood flow: validation against magnetic resonance imaging perfusion.

The ability to monitor cerebral blood flow (CBF) at the bedside is essential to managing critical-care patients with neurological emergencies. Diffuse correlation spectroscopy (DCS) is ideal because it is non-invasive, portable, and inexpensive. We investigated a near-infrared spectroscopy (NIRS) approach for converting DCS measurements into physiological units of blood flow. Using magnetic resonance imaging perfusion as a reference, we investigated the accuracy of absolute CBF measurements from a bolus-tracking NIRS method that used transient hypoxia as a flow tracer and hypercapnia-induced increases in CBF measured by DCS. Twelve participants (7 female, years) completed a hypercapnia protocol with simultaneous CBF recordings from DCS and arterial spin labeling (ASL). Nine participants completed the transient hypoxia protocol while instrumented with time-resolved NIRS. The estimate of baseline CBF was subsequently used to calibrate hypercapnic DCS data. Moderately strong correlations at baseline ( and ) and during hypercapnia ( and ) were found between CBF values from calibrated DCS and ASL (range 34 to ). Results demonstrated the feasibility of an all-optics approach that can both quantify CBF and perform continuous perfusion monitoring.

Real-time fMRI neurofeedback of the anterior insula using arterial spin labelling.

Arterial spin labelling (ASL) is the only non-invasive technique that allows absolute quantification of perfusion and is increasingly used in brain activation studies. Contrary to the blood oxygen level-dependent (BOLD) effect ASL measures the cerebral blood flow (CBF) directly. However, the ASL signal has a lower signal-to-noise ratio (SNR), than the BOLD signal, which constrains its utilization in neurofeedback studies. If successful, ASL neurofeedback can be used to aid in the rehabilitation of health conditions with impaired blood flow, for example, stroke. We provide the first ASL-based neurofeedback study incorporating a double-blind, sham-controlled design. A pseudo-continuous ASL (pCASL) approach with background suppression and 3D GRASE readout was combined with a real-time post-processing pipeline. The real-time pipeline allows to monitor the ASL signal and provides real-time feedback on the neural activity to the subject. In total 41 healthy adults (19-56 years) divided into three groups underwent a neurofeedback-based emotion imagery training of the left anterior insula. Two groups differing only in the explicitness level of instruction received real training and a third group received sham feedback. Only those participants receiving real feedback with explicit instruction showed significantly higher absolute CBF values in the trained region during neurofeedback than participants receiving sham feedback. However, responder analyses of percent signal change values show no differences in activation between the three groups. Persisting limitations, such as the lower SNR, confounding effects of arterial transit time and partial volume effects still impact negatively the implementation of ASL neurofeedback.

Test-retest reliability and time-of-day variations of perfusion imaging at rest and during a vigilance task.

Arterial spin-labeled perfusion and blood oxygenation level-dependent functional MRI are indispensable tools for noninvasive human brain imaging in clinical and cognitive neuroscience, yet concerns persist regarding the reliability and reproducibility of functional MRI findings. The circadian rhythm is known to play a significant role in physiological and psychological responses, leading to variability in brain function at different times of the day. Despite this, test-retest reliability of brain function across different times of the day remains poorly understood. This study examined the test-retest reliability of six repeated cerebral blood flow measurements using arterial spin-labeled perfusion imaging both at resting-state and during the psychomotor vigilance test, as well as task-induced cerebral blood flow changes in a cohort of 38 healthy participants over a full day. The results demonstrated excellent test-retest reliability for absolute cerebral blood flow measurements at rest and during the psychomotor vigilance test throughout the day. However, task-induced cerebral blood flow changes exhibited poor reliability across various brain regions and networks. Furthermore, reliability declined over longer time intervals within the day, particularly during nighttime scans compared to daytime scans. These findings highlight the superior reliability of absolute cerebral blood flow compared to task-induced cerebral blood flow changes and emphasize the importance of controlling time-of-day effects to enhance the reliability and reproducibility of future brain imaging studies.

MRI Evaluation of Microstructural and Perfusion Changes in Patients with Hemsensory Neurological Syndromes

Background: Hemisensory syndrome is characterized by a nondermatomal sensory deficit involving one half of the body. With the conventional imaging techniques, researches find low diagnostic yield in this condition; however, with the advancements in MRI imaging, there is hope to find the pathophysiological basis of hemisensory symptoms. Objective: To evaluate microstructural and perfusion changes in brain parenchyma in patients with hemisensory syndrome on MRI with diffusion tensor imaging (DTI) and arterial spin labeling (ASL). Material and Methods: A total of 20 patients with hemisensory symptoms and 10 age-matched controls were enrolled and divided in two study groups – a) case vs. control and b) affected vs. nonaffected cerebral hemisphere in cases. Quantification of absolute cerebral blood flow (aCBF), fractional anisotropy (FA), and mean diffusivity (MD) was done in both groups. Results: On ASL, there was significantly increased aCBF in thalamus on the contralateral-affected side. DTI revealed significantly decreased FA in the thalamus and increased FA in corona radiata of the affected side. There was a significant difference for MD of corona radiata between affected and nonaffected hemisphere. The mean value of MD in corona radiata is decreased on the affected side. Conclusion: Changes in advanced neuroimaging techniques like ASL and DTI along the pain processing pathway suggest an alteration in neuronal density and activity at the microstructural level. These findings may provide an insight into the etiopathogenesis of pain syndromes.

Abstract 12782: Serial Cerebral Hemodynamic Monitoring in Patients With HeartMate 3 Left Ventricular Assist Devices

Introduction: Left ventricular assist device (LVAD) implantation improves cardiopulmonary hemodynamics and vital organ perfusion, but cerebral blood flow is not routinely measured despite the clinical significance of neurologic complications. We aimed to quantify the short and long-term impact of LVAD on cerebral hemodynamics by serially monitoring patients before and after LVAD implantation. Hypothesis: We hypothesize that LVAD implantation improves dynamic measures of cerebral blood flow: cerebral autoregulation (CA) and cerebrovascular reactivity (CVR). Methods: 20 patients with advanced heart failure with planned LVAD implantation participated in serial cerebral hemodynamic monitoring: (1) <72-hours pre-implant, (2) <72-hours post-implant, (3) 14-days post-implant, and (4) 90-days post-implant. Cerebral blood flow velocity was measured at each visit by transcranial Doppler. CA, quantified by Mx index , characterized the relationship between blood pressure and cerebral blood flow. CVR quantified the cerebral hemodynamic reserve, based on the response to a hypercapnic stimulus (5% inhaled CO 2 ). Results: As compared to the pre-implant assessment, no change was noted in absolute cerebral blood flow velocity ( Figure 1a ). However, CA improved immediately post-implant (0.47 vs 0.26; p=0.0007), at 14-days (0.47 vs 0.33; p=0.007), and at 90-days (0.47 vs 0.31; p=0.03), Figure 1b . Pre-implant CVR was not significantly altered at 14-days (1.14 vs 1.70, p=0.25) but improved at 90-days (1.14 vs 2.11, p=0.03), Figure 1c . Conclusions: Despite no change in cerebral blood flow velocity, LVAD implantation improves dynamic measures of cerebral blood flow, CA and CVR. Future studies should include longer follow-up and correlate post-LVAD cerebral hemodynamics with clinically meaningful neurologic endpoints such as stroke and cognitive decline.

Psilocybin-induced changes in cerebral blood flow are associated with acute and baseline inter-individual differences

Research into the use of psilocybin for the treatment of psychiatric disorders is a growing field. Nevertheless, robust brain–behavior relationships linking psilocybin-induced brain changes to subjective drug-induced effects have not been established. Furthermore, it is unclear if the acute neural effects are dependent on individual heterogeneity in baseline characteristics. To address this, we assessed the effects of three oral doses of psilocybin vs. placebo on cerebral blood flow (CBF) using arterial spin labeling in healthy participants (N = 70; n = 31, 0.16 mg/kg; n = 10, 0.2 mg/kg; n = 29, 0.215 mg/kg). First, we quantified psilocybin-induced changes in relative and absolute CBF. Second, in an exploratory analysis, we assessed whether individual baseline characteristics and subjective psychedelic experience are associated with changes in CBF. Psychological and neurobiological baseline characteristics correlated with the psilocybin-induced reduction in relative CBF and the psilocybin-induced subjective experience. Furthermore, the psilocybin-induced subjective experience was associated with acute changes in relative and absolute CBF. The results demonstrated that inter-individual heterogeneity in the neural response to psilocybin is associated with baseline characteristics and shed light on the mechanisms underlying the psychedelic-induced altered state. Overall, these findings help guide the search for biomarkers, paving the way for a personalized medicine approach within the framework of psychedelic-assisted therapy.

Quantitative hemodynamic imaging: a method to correct the effects of optical properties on laser speckle imaging.

Studying cerebral hemodynamics may provide diagnostic information on neurological conditions. Wide-field imaging techniques, such as laser speckle imaging (LSI) and optical intrinsic signal imaging, are commonly used to study cerebral hemodynamics. However, they often do not account appropriately for the optical properties of the brain that can vary among subjects and even during a single measurement. Here, we describe the combination of LSI and spatial-frequency domain imaging (SFDI) into a wide-field quantitative hemodynamic imaging (QHI) system that can correct the effects of optical properties on LSI measurements to achieve a quantitative measurement of cerebral blood flow (CBF). We describe the design, fabrication, and testing of QHI. The QHI hardware combines LSI and SFDI with spatial and temporal synchronization. We characterized system sensitivity, accuracy, and precision with tissue-mimicking phantoms. With SFDI optical property measurements, we describe a method derived from dynamic light scattering to obtain absolute CBF values from LSI and SFDI measurements. We illustrate the potential benefits of absolute CBF measurements in resting-state and dynamic experiments. QHI achieved a 50-Hz raw acquisition frame rate with a field of view and flow sensitivity up to . The extracted SFDI optical properties agreed well with a commercial system (). The system showed high stability with low coefficients of variations over multiple sessions within the same day () and over multiple days (). When optical properties were considered, the in-vivo hypercapnia gas challenge showed a slight difference in CBF ( to 0.5% difference). The in-vivo resting-state experiment showed a change in CBF ranking for nine out of 13 animals when the correction method was applied to LSI CBF measurements. We developed a wide-field QHI system to account for the confounding effects of optical properties on CBF LSI measurements using the information obtained from SFDI.

Improved reliability of perfusion estimation in dynamic susceptibility contrast MRI by using the arterial input function from dynamic contrast enhanced MRI.

The arterial input function (AIF) plays a crucial role in estimating quantitative perfusion properties from dynamic susceptibility contrast (DSC) MRI. An important issue, however, is that measuring the AIF in absolute contrast-agent concentrations is challenging, due to uncertainty in relation to the measured -weighted signal, signal depletion at high concentration, and partial-volume effects. A potential solution could be to derive the AIF from separately acquired dynamic contrast enhanced (DCE) MRI data. We aim to compare the AIF determined from DCE MRI with the AIF from DSC MRI, and estimated perfusion coefficients derived from DSC data using a DCE-driven AIF with perfusion coefficients determined using a DSC-based AIF. AIFs were manually selected in branches of the middle cerebral artery (MCA) in both DCE and DSC data in each patient. In addition, a semi-automatic AIF-selection algorithm was applied to the DSC data. The amplitude and full width at half-maximum of the AIFs were compared statistically using the Wilcoxon rank-sum test, applying a 0.05 significance level. Cerebral blood flow (CBF) was derived with different AIF approaches and compared further. The results showed that the AIFs extracted from DSC scans yielded highly variable peaks across arteries within the same patient. The semi-automatic DSC-AIF had significantly narrower width compared with the manual AIFs, and a significantly larger peak than the manual DSC-AIF. Additionally, the DCE-based AIF provided a more stable measurement of relative CBF and absolute CBF values estimated with DCE-AIFs that were compatible with previously reported values. In conclusion, DCE-based AIFs were reproduced significantly better across vessels, showed more realistic profiles, and delivered more stable and reasonable CBF measurements. The DCE-AIF can, therefore, be considered as an alternative AIF source for quantitative perfusion estimations in DSC MRI.

Cortical microvascular blood flow velocity mapping by combining dynamic light scattering optical coherence tomography and two-photon microscopy.

The accurate large-scale mapping of cerebral microvascular blood flow velocity is crucial for a better understanding of cerebral blood flow (CBF) regulation. Although optical imaging techniques enable both high-resolution microvascular angiography and fast absolute CBF velocity measurements in the mouse cortex, they usually require different imaging techniques with independent system configurations to maximize their performances. Consequently, it is still a challenge to accurately combine functional and morphological measurements to co-register CBF speed distribution from hundreds of microvessels with high-resolution microvascular angiograms. We propose a data acquisition and processing framework to co-register a large set of microvascular blood flow velocity measurements from dynamic light scattering optical coherence tomography (DLS-OCT) with the corresponding microvascular angiogram obtained using two-photon microscopy (2PM). We used DLS-OCT to first rapidly acquire a large set of microvascular velocities through a sealed cranial window in mice and then to acquire high-resolution microvascular angiograms using 2PM. The acquired data were processed in three steps: (i)2PM angiogram coregistration with the DLS-OCT angiogram, (ii)2PM angiogram segmentation and graphing, and (iii)mapping of the CBF velocities to the graph representation of the 2PM angiogram. We implemented the developed framework on the three datasets acquired from the mice cortices to facilitate the coregistration of the large sets of DLS-OCT flow velocity measurements with 2PM angiograms. We retrieved the distributions of red blood cell velocities in arterioles, venules, and capillaries as a function of the branching order from precapillary arterioles and postcapillary venules from more than 1000 microvascular segments. The proposed framework may serve as a useful tool for quantitative analysis of large microvascular datasets obtained by OCT and 2PM in studies involving normal brain functioning, progression of various diseases, and numerical modeling of the oxygen advection and diffusion in the realistic microvascular networks.

Influence of oversimplifying the head anatomy on cerebral blood flow measurements with diffuse correlation spectroscopy.

Diffuse correlation spectroscopy (DCS) is an emerging optical modality for non-invasive assessment of an index of regional cerebral blood flow. By the nature of this noninvasive measurement, light must pass through extracerebral layers (i.e., skull, scalp, and cerebral spinal fluid) before detection at the tissue surface. To minimize the contribution of these extracerebral layers to the measured signal, an analytical model has been developed that treats the head as a series of three parallel and infinitely extending slabs (mimicking scalp, skull, and brain). The three-layer model has been shown to provide a significant improvement in cerebral blood flow estimation over the typically used model that treats the head as a bulk homogenous medium. However, the three-layer model is still a gross oversimplification of the head geometry that ignores head curvature, the presence of cerebrospinal fluid (CSF), and heterogeneity in layer thickness. Determine the influence of oversimplifying the head geometry on cerebral blood flow estimated with the three-layer model. Data were simulated with Monte Carlo in a four-layer slab medium and a three-layer sphere medium to isolate the influence of CSF and curvature, respectively. Additionally, simulations were performed on magnetic resonance imaging (MRI) head templates spanning a wide-range of ages. Simulated data were fit to both the homogenous and three-layer model for CBF. Finally, to mitigate the errors in potential CBF estimation due to the difficulty in defining layer thickness, we investigated an approach to identify an equivalent, "optimized" thickness via a pressure modulation. Both head curvature and failing to account for CSF lead to significant errors in the estimation of CBF. However, the effect of curvature and CSF on relative changes in CBF is minimal. Further, we found that CBF was underestimated in all MRI-templates, although the magnitude of these underestimations was highly influenced by small variations in the source and detector optode positioning. The optimized thickness obtained from pressure modulation did not improve estimation accuracy of CBF, although it did significantly improve the estimation accuracy of relative changes in CBF. In sum, these findings suggest that the three-layer model holds promise for improving estimation of relative changes in cerebral blood flow; however, estimations of absolute cerebral blood flow with the approach should be viewed with caution given that it is difficult to account for appreciable sources of error, such as curvature and CSF.

Test-retest reliability of 3D velocity-selective arterial spin labeling for detecting normal variations of cerebral blood flow

Velocity-selective inversion (VSI) based velocity-selective arterial spin labeling (VSASL) has been developed to measure cerebral blood flow (CBF) with low susceptibility to the prolonged arterial transit time and high sensitivity to brain perfusion signal. The purpose of this magnetic resonance imaging study is to evaluate the test-retest reliability of a VSI-prepared 3D VSASL protocol with whole-brain coverage to detect baseline CBF variations among cognitively normal participants in different brain regions. Coefficients of variation (CoV) of both absolute and relative CBF across scans or sessions, subjects, and gray matter regions were calculated, and corresponding intraclass correlation coefficients (ICC) were computed. The higher between-subject CoV of absolute CBF (13.4 ± 2.0%) over within-subject CoV (within-session: 3.8 ± 1.1%; between-session: 4.9 ± 0.9%) yielded moderate to excellent ICC (within-session: 0.88±0.08; between-session: 0.77±0.14) to detect normal variations of individual CBF. The higher between-region CoV of relative CBF (11.4 ± 3.0%) over within-region CoV (within-session: 2.3 ± 0.9%; between-session: 3.3 ± 1.0%) yielded excellent ICC (within-session: 0.92±0.06; between-session: 0.85±0.12) to detect normal variations of regional CBF. Age, blood pressure, end-tidal CO2, and hematocrit partially explained the variability of CBF across subjects. Together these results show excellent test-retest reliability of VSASL to detect both between-subject and between-region variations supporting its clinical utility.

Role of arterial spin labeling magnetic resonance perfusion in acute ischemic stroke

BackgroundArterial spin labeling (ASL) is a recently used magnetic resonance imaging (MRI) perfusion technique in acute cerebrovascular stroke conditions; it can detect the hypo perfused areas on basis of qualitative and quantitative measurements and also identify the area at risk known as penumbra by detecting the diffusion/perfusion mismatch. The purpose of this study was to assess the role of ASL perfusion technique in management of acute ischemic stroke and its ability to predict the clinical outcome of acute stroke patients. The study was prospectively carried out on 33 patients clinically presented with acute stroke from the first of August 2020 till the first of August 2021. All cases were clinically assessed by stroke consultant followed by brain imaging including conventional MRI and ASL perfusion technique, based upon which management was established. These imaging data were correlated with the clinical outcome after 3 months using Modified Rankin Scale.ResultsSixteen cases (48.48%) showed ischemic penumbra with diffusion perfusion mismatch with three cases presenting within the first 4 h managed by intravenous thrombolytic therapy and 13 cases presenting later than 4 h, 10 of whom were managed by endovascular intervention. The group with ischemic penumbra showed significant positive correlation with favorable clinical outcome while the group without ischemic penumbra showed significant positive correlation with poor clinical outcome. Quantitative ASL values were statistically significantly higher (p ≤ 0.05) in patients with favorable clinical outcome than those with poor clinical outcome. The estimated cut off values of ASL absolute cerebral blood flow and relative cerebral blood flow to predict favorable or poor outcome using ROC curve analysis were 19 ml/100gm/min and 74% compared to the contralateral side respectively.ConclusionThe use of MRI as a primary diagnostic tool in arterial ischemic stroke with the application of non-contrast ASL perfusion sequence allows precise detection of perfusion deficit and diffusion perfusion mismatch (penumbra) and provides a reliable insight into outcome prediction.

The value of arterial spin labelling (ASL) perfusion MRI in the assessment of post-treatment progression in adult glioma: A systematic review and meta-analysis.

The distinction between viable tumor and therapy-induced changes is crucial for the clinical management of patients with gliomas. This study aims to quantitatively assess the efficacy of arterial spin labeling (ASL) biomarkers, including relative cerebral blood flow (rCBF) and absolute cerebral blood flow (CBF), for the discrimination of progressive disease (PD) and treatment-related effects. Eight articles were included in the synthesis after searching the literature systematically. Data have been extracted and a meta-analysis using the random-effect model was subsequently carried out. Diagnostic accuracy assessment was also performed. This study revealed that there is a significant difference in perfusion measurements between groups with PD and therapy-induced changes. The rCBF yielded a standardized mean difference (SMD) of 1.25 [95% CI 0.75, 1.75] (p < .00001). The maximum perfusion indices (rCBFmax and CBFmax) both showed equivalent discriminatory ability, with SMD of 1.35 [95% CI 0.78, 1.91] (p < .00001) and 1.56 [95% CI 0.79, 2.33] (p < .0001), respectively. Similarly, accuracy estimates were comparable among ASL-derived metrices. Pooled sensitivities [95% CI] were 0.85 [0.67, 0.94], 0.88 [0.71, 0.96], and 0.93 [0.73, 0.98], and pooled specificities [95% CI] were 0.83 [0.71, 0.91], 0.83 [0.67, 0.92], 0.84 [0.67, 0.93], for rCBF, rCBFmax and CBFmax, respectively. Corresponding HSROC area under curve (AUC) [95% CI] were 0.90 [0.87, 0.92], 0.92 [0.89, 0.94], and 0.93 [0.90, 0.95]. These results suggest that ASL quantitative biomarkers, particularly rCBFmax and CBFmax, have the potential to discriminate between glioma progression and therapy-induced changes.

Precision estimates of Relative and Absolute Cerebral Blood Flow in Alzheimer’s disease and Cognitively Normal individuals

AbstractBackgroundAlzheimer’s disease is characterized by regional reductions in cerebral blood flow (CBF) and the gold standard for measuring CBF is [15O]H2O PET. Recently, proxies of relative CBF, derived from the early distribution phase of amyloid‐β and tau tracers, have gained attention. It has been hypothesized that relative CBF is likely to have higher precision (but not accuracy) than absolute CBF, as global variations in CBF are cancelled out. The present study assessed precision of [15O]H2O PET derived relative and absolute CBF measures, and compared them with relative CBF proxies estimated from [18F]florbetapir and [18F]flortaucipir scans.MethodDynamic [15O]H2O, [18F]florbetapir and [18F]flortaucipir test‐retest (TRT) PET datasets were included, consisting of eleven cognitively normal (CN) individuals for [15O]H2O, four CN and five AD participants for [18F]florbetapir, and six CN and eight AD participants for [18F]flortaucipir. [15O]H2O data were analysed using the standard single tissue compartment model and [18F]florbetapir and [18F]flortaucipir using the simplified reference tissue model (SRTM). Relative CBF (i.e. K1/K1’) was derived from absolute CBF (i.e. K1 of [15O]H2O) or estimated using SRTM (i.e. R1), in all cases using cerebellar cortex as reference tissue. CBF values were obtained for 22 cortical grey matter regions and TRT variability (eq.1) was calculated for all metrics. Differences (%) between test and retest measures were assessed using Bland‐Altman analysis and TRT variability for different tracers and between diagnostic groups were compared using Wilcoxon Signed‐Rank and Mann‐Whitney U‐tests.ResultAverage differences (M±SD) between test and retest measures were small for relative measures, [15O]H2O K1/K1’:‐2.0±7.8%, [18F]florbetapir R1:‐1.7±4.1%, [18F]flortaucipir R1:‐0.1±4.2%, but somewhat larger for [15O]H2O K1:‐5.7±14.6%,(Fig.1). In case of [15O]H2O, TRT variability was lower for K1/K1’ than for K1 (p&lt;0.001). Furthermore, [18F]florbetapir and [18F]flortaucipir derived R1 showed lower TRT variability than [15O]H2O K1/K1’ (p&lt;0.001). Only for [18F]flortaucipir, TRT variability was higher in the AD compared with the CN group.ConclusionRelative CBF has higher precision than absolute CBF derived from [15O]H2O PET scans. Furthermore, relative CBF proxies derived from commonly used amyloid‐β and tau tracers appear to have an even higher precision, possibly due to the compensatory effect of extraction fraction and/or the older scanner used for [15O]H2O scans.

Precision estimates of Relative and Absolute Cerebral Blood Flow in Alzheimer’s disease and Cognitively Normal individuals

AbstractBackgroundAlzheimer’s disease is characterized by regional reductions in cerebral blood flow (CBF) and the gold standard for measuring CBF is [15O]H2O PET. Recently, proxies of relative CBF, derived from the early distribution phase of amyloid‐β and tau tracers, have gained attention. It has been hypothesized that relative CBF is likely to have higher precision (but not accuracy) than absolute CBF, as global variations in CBF are cancelled out. The present study assessed precision of [15O]H2O PET derived relative and absolute CBF measures, and compared them with relative CBF proxies estimated from [18F]florbetapir and [18F]flortaucipir scans.MethodDynamic [15O]H2O, [18F]florbetapir and [18F]flortaucipir test‐retest (TRT) PET datasets were included, consisting of eleven cognitively normal (CN) individuals for [15O]H2O, four CN and five AD participants for [18F]florbetapir, and six CN and eight AD participants for [18F]flortaucipir. [15O]H2O data were analysed using the standard single tissue compartment model and [18F]florbetapir and [18F]flortaucipir using the simplified reference tissue model (SRTM). Relative CBF (i.e. K1/K1’) was derived from absolute CBF (i.e. K1 of [15O]H2O) or estimated using SRTM (i.e. R1), in all cases using cerebellar cortex as reference tissue. CBF values were obtained for 22 cortical grey matter regions and TRT variability (eq.1) was calculated for all metrics. Differences (%) between test and retest measures were assessed using Bland‐Altman analysis and TRT variability for different tracers and between diagnostic groups were compared using Wilcoxon Signed‐Rank and Mann‐Whitney U‐tests.ResultAverage differences (M±SD) between test and retest measures were small for relative measures, [15O]H2O K1/K1’:‐2.0±7.8%, [18F]florbetapir R1:‐1.7±4.1%, [18F]flortaucipir R1:‐0.1±4.2%, but somewhat larger for [15O]H2O K1:‐5.7±14.6%,(Fig.1). In case of [15O]H2O, TRT variability was lower for K1/K1’ than forK1 (p&lt;0.001). Furthermore, [18F]florbetapir and [18F]flortaucipir derived R1 showed lower TRT variability than [15O]H2O K1/K1’ (p&lt;0.001). Only for [18F]flortaucipir, TRT variability was higher in the AD compared with the CN group.ConclusionRelative CBF has higher precision than absolute CBF derived from [15O]H2O PET scans. Furthermore, relative CBF proxies derived from commonly used amyloid‐β and tau tracers appear to have an even higher precision, possibly due to the compensatory effect of extraction fraction and/or the older scanner used for [15O]H2O scans.

Precision estimates of relative and absolute cerebral blood flow in Alzheimer’s disease and cognitively normal individuals

Alzheimer’s disease is characterized by regional reductions in cerebral blood flow (CBF). Although the gold standard for measuring CBF is [15O]H2O PET, proxies of relative CBF, derived from the early distribution phase of amyloid and tau tracers, have gained attention. The present study assessed precision of [15O]H2O derived relative and absolute CBF, and compared precision of these measures with that of (relative) CBF proxies. Dynamic [15O]H2O, [18F]florbetapir and [18F]flortaucipir PET test-retest (TrT) datasets with eleven, nine and fourteen subjects, respectively, were included. Analyses were performed using an arterial input model and/or a simplified reference tissue model, depending on the data available. Relative CBF values (i.e. K1/K1′ and/or R1) were obtained using cerebellar cortex as reference tissue and TrT repeatability (i.e. precision) was calculated and compared between tracers, parameters and clinical groups. Relative CBF had significantly better TrT repeatability than absolute CBF derived from [15O]H2O (r = −0.53), while best TrT repeatability was observed for [18F]florbetapir and [18F]flortaucipir R1 (r = −0.23, r = −0.33). Furthermore, only R1 showed, better TrT repeatability for cognitively normal individuals. High precision of CBF proxies could be due to a compensatory effect of the extraction fraction, although changes in extraction fraction could also bias these proxies, but not the gold standard.

Reduced cortical cerebral blood flow in antipsychotic-free first-episode psychosis and relationship to treatment response.

Altered cerebral blood flow (CBF) has been found in people at risk for psychosis, with first-episode psychosis (FEP) and with chronic schizophrenia (SCZ). Studies using arterial spin labelling (ASL) have shown reduction of cortical CBF and increased subcortical CBF in SCZ. Previous studies have investigated CBF using ASL in FEP, reporting increased CBF in striatum and reduced CBF in frontal cortex. However, as these people were taking antipsychotics, it is unclear whether these changes are related to the disorder or antipsychotic treatment and how they relate to treatment response. We examined CBF in FEP free from antipsychotic medication (N = 21), compared to healthy controls (N = 22). Both absolute and relative-to-global CBF were assessed. We also investigated the association between baseline CBF and treatment response in a partially nested follow-up study (N = 14). There was significantly lower absolute CBF in frontal cortex (Cohen's d = 0.84, p = 0.009) and no differences in striatum or hippocampus. Whole brain voxel-wise analysis revealed widespread cortical reductions in absolute CBF in large cortical clusters that encompassed occipital, parietal and frontal cortices (Threshold-Free Cluster Enhancement (TFCE)-corrected <0.05). No differences were found in relative-to-global CBF in the selected region of interests and in voxel-wise analysis. Relative-to-global frontal CBF was correlated with percentage change in total Positive and Negative Syndrome Scale after antipsychotic treatment (r = 0.67, p = 0.008). These results show lower cortical absolute perfusion in FEP prior to starting antipsychotic treatment and suggest relative-to-global frontal CBF as assessed with magnetic resonance imaging could potentially serve as a biomarker for antipsychotic response.

Pulsed Arterial Spin Labeling and Segmented Brain Volumetry in the Diagnostic Evaluation of Frontotemporal Dementia, Alzheimer’s Disease and Mild Cognitive Impairment

Background: Previous studies suggest that brain atrophy can not only be defined by its morphological extent, but also by the cerebral blood flow (CBF) within a certain area of the brain, including white and gray matter. The aim of this study is to investigate known atrophy patterns in different forms of dementia and to compare segmented brain volumetrics and pulsed arterial spin labeling (pASL) data to explore the correlation between brain maps with atrophy and this non-contrast-enhanced brain-perfusion method. Methods: Our study comprised 17 patients with diagnosed cognitive impairment (five Alzheimer’s disease = AD, five frontotemporal dementia = FTD, seven mild cognitive impairment = MCI) and 19 healthy control subjects (CO). All patients and controls underwent 4D-pASL brain-perfusion MR imaging and T1w MPRAGE. The data were assessed regarding relative brain volume on the basis of 286 brain regions, and absolute and relative cerebral blood flow (CBF/rCBF) were derived from pASL data in the corresponding brain regions. Mini-Mental State Examination (MMSE) was performed to assess cognitive functions. Results: FTD patients demonstrated significant brain atrophy in 43 brain regions compared to CO. Patients with MCI showed significant brain atrophy in 18 brain regions compared to CO, whereas AD patients only showed six brain regions with significant brain atrophy compared to CO. There was good correlation of brain atrophy and pASL perfusion data in five brain regions of patients with diagnosed FTD, especially in the superior temporal gyrus (r = 0.900, p = 0.037), the inferior frontal white matter (pars orbitalis; r = 0.968, p = 0.007) and the thalami (r = 0.810, p = 0.015). Patients with MCI demonstrated a correlation in one brain region (left inferior fronto-occipital fasciculus; r = 0.786, p = 0.036), whereas patients with diagnosed AD revealed no correlation. Conclusions: pASL can detect affected brain regions in cognitive impairment and corresponds with brain atrophy, especially for patients suffering from FTD and MCI. However, there was no correlation of perfusion alterations and brain atrophy in AD. pASL perfusion might thus represent a promising tool for noninvasive brain-perfusion evaluation in specific dementia subtypes as a complimentary imaging-based bio marker in addition to brain volumetry.

Concurrent CBF and BOLD fMRI with dual-echo spiral simultaneous multi-slice acquisitions at 7T

Measurement of cerebral blood flow (CBF) using the Arterial Spin Labeling (ASL) technique is a desirable fMRI approach due to the higher specificity of CBF to the site of neural activation. However, ASL has inherent limitations, such as a low signal-to-noise ratio (SNR) and low coverage/resolution due to the limited readout window following the labeling. Recently, ASL has been implemented at ultra-high field (UHF) strengths in an attempt to mitigate the SNR challenges. Even though ASL intrinsically allows concurrent acquisition of CBF and BOLD contrasts, a compromise in the echo time (TE) for either of the contrasts is inevitable with single-echo acquisitions. Long durations of the Cartesian EPI readout do not allow for multi-echo acquisitions for resolutions ≤2 mm where both contrasts can be acquired at their optimal TE at UHF. With its higher acquisition efficiency, single-shot spiral imaging provides a promising alternative to EPI, and with a dual-echo, out-in trajectory allows both CBF and BOLD contrasts to be acquired at their respective optimal TE. In this work, we implemented a dual-echo spiral out-in ASL sequence with simultaneous multi-slice (SMS) readout for increased coverage, and validated its application to fMRI with a visuomotor paradigm. Conventional Cartesian EPI acquisitions with matched parameters served as a reference. The dual-echo spiral ASL acquisitions resulted in robust CBF and BOLD activations maps. The absolute and relative CBF changes measured with the dual-echo spiral readout were in agreement with previous reports in the literature as well as the reference Cartesian acquisitions. The BOLD response amplitude was higher compared to the Cartesian acquisitions, attributable to a more optimal TE of the second echo. In conclusion, dual-echo spiral out-in SMS acquisition shows promise for concurrent acquisitions of BOLD and non-BOLD contrasts that require a short TE, with no loss in temporal resolution.

Cerebral Perfusion and Sensory Testing Results Differ in Interstitial Cystitis/Bladder Pain Syndrome Patients with and without Fibromyalgia: A Site-Specific MAPP Network Study.

PurposeFibromyalgia is a common co-morbidity in patients with interstitial cystitis/bladder pain syndrome. Quantitative sensory testing measures and regional cerebral blood flow measures have been noted to differ from healthy controls in both subjects with fibromyalgia and those with interstitial cystitis when studied independently. The present study examined such measures in subjects with the diagnosis of interstitial cystitis both with and without the co-diagnosis of fibromyalgia to determine whether differences in these measures may be associated with co-morbidity.Patients and MethodsFemale subjects with the diagnosis of interstitial cystitis with (n = 15) and without (n = 19) the co-diagnosis of fibromyalgia as well as healthy control subjects (n = 41) underwent quantitative sensory testing. A subset of these patients (9 with and 9 without fibromyalgia) underwent brain perfusion studies using arterial spin labeled functional magnetic resonance imaging. An analysis was performed of absolute regional cerebral blood flow of regions-of-interest when experiencing a full bladder compared with an empty bladder.ResultsSubjects with both interstitial cystitis and fibromyalgia were more hypersensitive than those without fibromyalgia as well as healthy controls in most sensory measures except heat. Subjects with interstitial cystitis, but no fibromyalgia, differed from healthy controls only in toleration of the ischemic forearm task. Other co-morbidities were more common in those subjects with both interstitial cystitis and fibromyalgia. Bladder fullness was associated with significantly greater whole brain gray matter blood flow in subjects with interstitial cystitis and fibromyalgia when compared with that of subjects with interstitial cystitis without fibromyalgia. Examination of regional cerebral blood flow in individual regions-of-interest demonstrated statistically significant differences between the subjects with interstitial cystitis with and those without fibromyalgia bilaterally in the thalamus, amygdala and hippocampus, as well as the right prefrontal cortex and greater responsiveness to changes in bladder fullness in the insula.ConclusionQuantitative sensory testing and brain perfusion data support that there are two phenotypes of interstitial cystitis patients, which can be differentiated by a co-diagnosis of fibromyalgia. This may affect responsiveness to treatment and suggest the utility of stratifying interstitial cystitis patients according to their co-morbidities.