Cerebral Blood Flow Estimates Research Articles

Screening for Cognitive Impairment by Model-Assisted Cerebral Blood Flow Estimation.

Alzheimer's disease (AD) is a progressive and debilitating neurodegenerative disease; a major health concern in the ageing population with an estimated prevalence of 46 million dementia cases worldwide. Early diagnosis is therefore crucial so mitigating treatments can be initiated at an early stage. Cerebral hypoperfusion has been linked with blood-brain barrier dysfunction in the early stages of AD, and screening for chronic cerebral hypoperfusion in individuals has been proposed for improving the early diagnosis of AD. However, ambulatory measurements of cerebral blood flow are not routinely carried out in the clinical setting. In this study, we combine physiological modeling with Holter blood pressure monitoring and carotid ultrasound imaging to predict 24-h cerebral blood flow (CBF) profiles in individuals. One hundred and three participants [53 with mild cognitive impairment (MCI) and 50 healthy controls] underwent model-assisted prediction of 24-h CBF. Model-predicted CBF and neuropsychological tests were features in lasso regression models for MCI diagnosis. A CBF-enhanced classifier for diagnosing MCI performed better, area-under-the-curve (AUC) = 0.889 (95%-CI: 0.800 to 0.978), than a classifier based only on the neuropsychological test scores, AUC = 0.818 (95%-CI: 0.643 to 0.992). An additional cohort of 25 participants (11 MCI and 14 healthy) was recruited to perform model validation by arterial spin-labeling magnetic resonance imaging, and to establish a link between measured CBF that predicted by the model. Ultrasound imaging and ambulatory blood pressure measurements enhanced with physiological modeling can improve MCI diagnosis accuracy.

Semi-quantitative cerebral blood flow parameters derived from non-invasive [15O]H2O PET studies

Quantification of regional cerebral blood flow (CBF) using [15O]H2O positron emission tomography (PET) requires the use of an arterial input function. Arterial sampling, however, is not always possible, for example in ill-conditioned or paediatric patients. Therefore, it is of interest to explore the use of non-invasive methods for the quantification of CBF. For validation of non-invasive methods, test–retest normal and hypercapnia data from 15 healthy volunteers were used. For each subject, the data consisted of up to five dynamic [15O]H2O brain PET studies of 10 min and including arterial sampling. A measure of CBF was estimated using several non-invasive methods earlier reported in literature. In addition, various parameters were derived from the time-activity curve (TAC). Performance of these methods was assessed by comparison with full kinetic analysis using correlation and agreement analysis. The analysis was repeated with normalization to the whole brain grey matter value, providing relative CBF distributions. A reliable, absolute quantitative estimate of CBF could not be obtained with the reported non-invasive methods. Relative (normalized) CBF was best estimated using the double integration method.

Early-phase 18F-AV-45 PET Imaging can Detect Crossed Cerebellar Diaschisis Following Carotid Artery Stenosis and Cerebral Hypoperfusion.

Carotid artery stenosis (CAS) may induce cerebral hypoperfusion. Early-phase 18F-Florbetapir (AV-45/Amyvid, 18F-AV-45) positron emission tomography (PET) imaging can provide perfusion-like property (pAV-45) for the estimation of cerebral blood flow (CBF). Supra-tentorial lesions may cause decreased blood flow and metabolism in the contralateral cerebellum known as crossed cerebellar diaschisis (CCD). The aim was to study the occurrence of CCD after CAS using pAV-45 PET. Eleven healthy controls and 21 patients with unilateral CAS were studied. All subjects underwent 18F-AV-45 PET imaging and arterial spin labeling (ASL) CBF magnetic resonance perfusion imaging. The pAV-45 and ASL CBF values were first correlated. Then, cerebral and cerebellar hypoperfusion volume was analyzed. The cerebral and cerebellar perfusion asymmetry indices (AIs) were calculated from the pAV-45 standard uptake value ratios (SUVRs) of bilateral cerebral and cerebellar cortices, respectively. We found that pAV-45 SUVR was significantly correlated to ASL CBF (p<0.0001, r=0.5731). The AI of cerebellar perfusion was negatively correlated to that of cerebral perfusion (p<0.0001, r=-0.8751). Multiple linear regression showed the cerebral AI (p<0.0001) and hypoperfusion volume (p=0.02) but not the infarction severity and CAS degree significantly correlated to cerebellar AI. If the lower limit of 95% confidence interval of cerebellar AI in healthy controls was set as cut-off for positive CCD, the occurrence of CCD correlated to infarction severity in CAS patients (p=0.03). Our results suggest pAV-45 is reliable to study CBF change. Under unilateral CAS, cerebral AI and hypoperfusion severity may determine the occurrence of CCD.

Enhancement of automated blood flow estimates (ENABLE) from arterial spin‐labeled MRI

To validate a multiparametric automated algorithm-ENhancement of Automated Blood fLow Estimates (ENABLE)-that identifies useful and poor arterial spin-labeled (ASL) difference images in multiple postlabeling delay (PLD) acquisitions and thereby improve clinical ASL. ENABLE is a sort/check algorithm that uses a linear combination of ASL quality features. ENABLE uses simulations to determine quality weighting factors based on an unconstrained nonlinear optimization. We acquired a set of 6-PLD ASL images with 1.5T or 3.0T systems among 98 healthy elderly and adults with mild cognitive impairment or dementia. We contrasted signal-to-noise ratio (SNR) of cerebral blood flow (CBF) images obtained with ENABLE vs. conventional ASL analysis. In a subgroup, we validated our CBF estimates with single-photon emission computed tomography (SPECT) CBF images. ENABLE produced significantly increased SNR compared to a conventional ASL analysis (Wilcoxon signed-rank test, P < 0.0001). We also found the similarity between ASL and SPECT was greater when using ENABLE vs. conventional ASL analysis (n = 51, Wilcoxon signed-rank test, P < 0.0001) and this similarity was strongly related to ASL SNR (t = 24, P < 0.0001). These findings suggest that ENABLE improves CBF image quality from multiple PLD ASL in dementia cohorts at either 1.5T or 3.0T, achieved by multiparametric quality features that guided postprocessing of dementia ASL. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:647-655.

APOE ε4 ALLELE EFFECT ON WHITE AND GRAY MATTER PERFUSION IN COGNITIVELY NORMAL AND MCI GROUPS

Cerebral perfusion in both white and gray matter may be an indicator of vascular dysfunction and cognition decline. In this study, simultaneous estimates of cerebral blood flow (CBF) and arterial transit time (ATT) using multiple inversion time arterial spin labeling (ASL) was analyzed in cognitively normal and mild cognitive impairment (MCI) groups. Lower CBF and shorter ATT in APOE ε4 carriers may indicate cerebrovascular functional disorder that impacts cognitive function. 87 subjects (62 cognitively normal (23% ε4+) and 25 MCI (48% ε4+); 23M/64F; age: 63.9±7.7) underwent baseline brain MRI exams as part of several on-going studies within the Wake Forest AD Center, including pseudo-continuous ASL to estimate voxel-wise whole brain CBF and ATT in white and gray matters using a partial volume correction. An example CBF and ATT maps are shown in Figure 1. All ASL images were co-registered to T1 weighted structural images and normalized into a study specific template. Age, Sex, BMI, and HbA1C were adjusted and 2-way ANOVA was performed for each voxel. A minimum cluster size was determined with p<0.05 and α=0.05. APOE ε4 carriers showed reduced CBF in a white matter cluster and four gray matter clusters as shown in Figure 2. The white matter hypo-perfusion cluster locates mainly in left sub-lobar region and extends over temporal and parietal lobes. Four small clusters in gray matter are in left hippocampus, thalamus, right lingual, and right hippocampus and amygdala (Table 1). Although were not statistically significant, ATT values measured in the clusters representing lower blood flow are also shorter in the ε4 carriers (Table 2). In addition, the group without ε4 Allele showed a trend of compensatory increased blood flow in MCI while that with ε4 Allele had impaired blood flow. In this small pilot study sample, lower CBF and shortened ATT were observed among APOE ε4 carriers in both white and gray matter and did not significantly differ by cognitive status. These data suggest evidence of that a perfusion abnormality indicative of flow dynamics of arterial stiffness / arteriolosclerosis are seen among ε4 carriers that may contribute to cerebrovascular disorders. CBF and ATT maps in GM and WM from a representative subject (82 yr. old, F). The partial volume fraction of 0.2 was applied to make the maps. Clusters in white and gray matters representing lower blood flow in the group with APOE ε4 Allele.

Dynamic Susceptibility Contrast MRI at 7 T: Tail-Scaling Analysis and Inferences About Field Strength Dependence.

Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) following bolus injection of gadolinium contrast agent (CA) is widely used for the estimation of brain perfusion parameters such as cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) for both clinical and research purposes. Although it is predicted that DSC-MRI will have superior performance at high magnetic field strengths, to the best of our knowledge, there are no reports of 7 T DSC-MRI in the literature. It is plausible that the transfer of DSC-MRI to 7 T may be accompanied by increased R2* relaxivity in tissue and a larger difference in ΔR2*-versus-concentration relationships between tissue and large vessels. If not accounted for, this will subsequently result in apparent CBV and CBF estimates that are higher than those reported previously at lower field strengths. The aims of this study were therefore to assess the feasibility of 7 T DSC-MRI and to investigate the apparent field-strength dependence of CBV and CBF estimates. In total, 8 healthy volunteers were examined using DSC-MRI at 7 T. A reduced CA dose of 0.05 mmol/kg was administered to decrease susceptibility artifacts. CBV, CBF, and MTT maps were calculated using standard DSC-MRI tracer-kinetic theory. Subject-specific arterial partial volume correction factors were obtained using a tail-scaling approach. Compared with literature values obtained using the tail-scaling approach at 1.5 T and 3 T, the CBV and CBF values of the present study were found to be further overestimated. This observation is potentially related to an inferred field-strength dependence of transverse relaxivities, although issues related to the CA dose must also be considered.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging Suggests Normal Perfusion in Normal-Appearing White Matter in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system and has been associated with reduced perfusion in normal-appearing white matter (NAWM). The magnitude of this hypoperfusion is unclear. The present study aims to quantify NAWM perfusion with dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in patients with relapsing-remitting (RR) MS and in a control group. The statistical power of a DCE-MRI acquisition to reveal hypoperfusion in MS was estimated using a Monte Carlo simulation: synthetic tissue curves with a contrast-to-noise ratio of 8 were generated for MS patients and control group using perfusion values reported in previous studies. A compartment-uptake model was fitted to these curves, yielding estimates of cerebral blood flow (CBF), cerebral blood volume (CBV), and permeability-surface area product (PS). This was repeated 1000 times. Mean and standard deviation of the resulting distributions were used to calculate the statistical power of a DCE-MRI study to detect perfusion differences between 16 control subjects and 24 MS subjects.In an institutional review board-approved study, patients with RR-MS (n = 24; mean age, 36 years; 17 women, mean Enhanced Disability Status Scale score, 3.25) and patients without history or symptoms of neurological disorder (n = 16; mean age, 49 years; 9 women) underwent a DCE-MRI examination with a previously established MRI protocol (3D SPGR sequence; 2.1 seconds temporal resolution; 44 slices; spatial resolution, 1.7 × 1.7 × 3 mm). Regions were defined manually in the middle cerebral artery; in the frontal, periventricular, and occipital NAWM; in the pons; and in the thalamus, and CBF, CBV, and PS were quantified using a compartment-uptake model.Parameter differences between MS and control groups were evaluated using a mixed linear model with subjects as random effect and controlling for age and sex. A P value of less than 0.05 was considered to indicate statistical significance. For all but one of previously reported effect sizes, the simulation study estimated a statistical power of 80% to 100% to detect reduced CBF in MS. In the patient study, mean (standard deviation) CBF in NAWM was 11.0 (15.1) and 10.4 (8.2) mL/100 mL per minute in the MS and control groups, respectively. Mean CBV in NAWM was 0.50 (0.45) mL/100 mL in the MS group and 0.48 (0.28) mL/100 mL in the control group. Mean values of PS in NAWM were 0.002 mL (0.027)/100 mL per minute in the control group and -0.001 (0.015) mL/100 mL per minute in the MS patients. Differences between patient groups were not statistically significant for CBF, CBV, mean transit time, and PS (P = 0.44, P = 0.20, P = 0.78, P = 0.66, respectively). In both groups, the influence of age on any parameter was nonsignificant. Cerebral blood flow and CBV in the thalamus and pons were significantly higher than in NAWM regions (P < 1e-4); mean transit time was significantly shorter than in NAWM (P < 1e-4). Permeability-surface area product was not significantly different from zero (P > 0.25) in all evaluated regions. Despite high statistical power, we could not confirm previous reports of NAWM hypoperfusion in MS. This indicates that, at least in our patient cohort, potential hypoperfusion is much less pronounced than reported in previous studies.

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

ObjectiveA new method of delay time estimation was proposed to measure precise cerebral blood flow (CBF) and arterial-to-capillary blood volume (V0) using 15O-water PET.MethodsNineteen patients with unilateral arterial stenoocclusive lesions were studied to evaluate hemodynamic status before treatment. The delay time of each pixel was calculated using least squares fitting with an arterial blood input curve adjusted to the internal carotid artery counts at the skull base. Pixel-by-pixel delay estimation provided a delay map image that could be used for precise calculation of CBF and V0 using a one-tissue compartment model, and the values from this method were compared with those from the slice-by-slice correction method.ResultsThe affected side showed a longer delay time than the contralateral cerebral hemisphere. Although the mean cortical CBF values were not different between the two methods, the slice-by-slice delay correction overestimated CBF in the hypo perfused area. The scatter plot of V0 pixel values showed significant difference between the two correction methods where the slice-by-slice delay correction significantly overestimated V0 in the whole brain (P < 0.05).ConclusionPixel-by-pixel delay correction provides delay images as well as better estimation of CBF and V0, thus offering useful and beneficial information for the treatment of cerebrovascular disease.

Cerebral Blood Flow and Aβ-Amyloid Estimates by WARM Analysis of [11C]PiB Uptake Distinguish among and between Neurodegenerative Disorders and Aging.

Background: We report results of the novel Washout Allometric Reference Method (WARM) that uses estimates of cerebral blood flow and amyloid load from the same [11C]Pittsburgh Compound B ([11C]PiB) retention maps in brain to distinguish between patients with different forms dementia, including Alzheimer’s disease, and healthy volunteers. The method introduces two approaches to the identification of brain pathology related to amyloid accumulation, (1) a novel analysis of amyloid binding based on the late washout of the tracer from brain tissue, and (2) the simultaneous estimation of absolute cerebral blood flow indices (sCBF) from the early accumulation of the tracer in brain tissue.Objective: We tested the hypothesis that a change of cerebral blood flow is correlated with the degree of tracer [11C]PiB retention, reflecting dendritic spine pathology and consequent inhibition of brain energy metabolism and reduction of blood flow by neurovascular coupling in neurodegenerative disorders, including Alzheimer’s disease.Methods: Previously reported images of [11C]PiB retention in brain of 29 subjects with cognitive impairment or dementia [16 Alzheimer’s Disease (AD), eight subjects with dementia with Lewy bodies (DLB), five patients with frontotemporal lobar degeneration (FTLD), five patients with mild cognitive impairment, and 29 age-matched healthy control subjects (HC)], underwent analysis of PiB delivery and retention by means of WARM for quantitation of [11C]PiB’s binding potentials (BPND) and correlated surrogate cerebral blood flow (sCBF) estimates, based on the [11C]PiB images, compared to estimates by conventional Standard Uptake Value Ratio (SUVR) of [11C]PiB retention with cerebellum gray matter as reference. Receiver Operating Characteristics (ROC) revealed the power of discrimination among estimates.Results: For AD, the discriminatory power of [11C]PiB binding potential (BPND) by WARM exceeded the power of SUVR that in turn exceeded the power of sCBF estimates. Differences of [11C]PiB binding and sCBF measures between AD and HC both were highly significant (p < 0.001). For all the dementia groups as a whole, sCBF estimates revealed the greatest discrimination between the patient and HC groups. WARM resolves a major issue of amyloid load quantification with [11C]PiB in human brain by determining absolute sCBF and amyloid load measures from the same images. The two parameter approach provides key discriminary information in AD for which [11C]PiB traditionally is used, as well as for the distinct flow deficits in FTLD, and the marked parietal and occipital lobe flow deficits in DLB.Conclusion: We conclude that WARM yields estimates of two important variables that together discriminate among patients with dementia, including AD, and healthy volunteers, with ROC that are superior to conventional methods of analysis. The distinction between estimates of flow and amyloid load from the same dynamic emission tomograms provides valuable pathogenetic information.

Noninvasive Measurement of Cerebral Blood Flow Under Anesthesia Using Arterial Spin Labeling MRI: A Pilot Study.

Cerebral ischemia plays a major role in pathophysiology of the injured brain. Most of the currently available methods of cerebral blood flow (CBF) monitors are either indirect measure of CBF or needing radioactive agents for data acquisition. Arterial spin labeling magnetic resonance imaging (ASL-MRI) is a noninvasive method of measuring CBF. The aim of our study was to determine the differences in the CBF values between propofol and sevoflurane anesthesia using ASL-MRI technique in mechanically ventilated patients with cerebrovascular disease. After ethics board approval and informed consent, we measured CBF in 4 patients with moyamoya disease, using a pseudo-continuous 3D ASL sequence available on a 3.0 T MRI scanner. Patients were anesthetized first with sevoflurane (1 MAC) and then anesthesia was converted to total intravenous anesthesia with propofol (100 to 125 μg/kg/min). When the patient was in a steady state with respect to anesthesia and normocapnia (baseline PETCO2), CBF was measured under both sevoflurane and propofol anesthesia. Quantitative estimation of both global and regional CBF was successfully performed in all patients. The mean global CBF in gray and white matter of all patients under propofol anesthesia were 38.4 and 31.6 mL/100 g/min, respectively. Similar values under sevoflurane anesthesia were 56.6 mL/100 g/min for gray matter and 42.5 mL/100 g/min for white matter. ASL-MRI is a feasible, noninvasive method of quantitative estimation of global and regional CBF in mechanically ventilated patients under anesthesia. In this pilot study CBF was consistently greater with sevoflurane than with propofol.

Implication of cerebral circulation time in intracranial stenosis measured by digital subtraction angiography on cerebral blood flow estimation measured by arterial spin labeling.

Arterial spin labeling (ASL) magnetic resonance imaging to assess cerebral blood flow (CBF) is of increasing interest in basic research and in diagnostic applications, since ASL provides similar information to positron emission tomography about perfusion in vascular territories. However, in patients with steno-occlusive arterial disease (SOAD), CBF as measured by ASL might be underestimated due to delayed bolus arrival, and thus increased spin relaxation. We aimed to estimate the extent to which bolus arrival time (BAT) was delayed in patients with SOAD and whether this resulted in underestimation of CBF. BAT was measured using digital subtraction angiography (DSA) in ten patients with high-grade stenosis of the middle carotid artery (MCA). Regional CBF was assessed with pseudocontinuous ASL. BATs were nonsignificantly prolonged in the stenotic hemisphere 4.1±2.0 s compared with the healthy hemisphere 3.3±0.9 s; however, there were substantial individual differences on the stenotic side. CBF in the anterior and posterior MCA territories were significantly reduced on the stenotic hemisphere. Severe stenosis was correlated with longer BAT and lower quantified CBF. ASL-based perfusion measurement involves a race between the decay of the spins and the delivery of labeled blood to the region of interest. Special caution is needed when interpreting CBF values quantified in individuals with altered blood flow and delayed circulation times. However, from a clinician's point of view, an accentuation of hypoperfusion (even if caused by underestimation of CBF due to prolonged BATs) might be desirable since it indexes potentially harmful physiologic deficits.

Measurement of cerebral blood flow using phase contrast magnetic resonance imaging and duplex ultrasonography

Phase contrast magnetic resonance imaging (PC-MRI) and color-coded duplex ultrasonography (CDUS) are commonly used for measuring cerebral blood flow in the internal carotid (ICA) and vertebral arteries. However, agreement between the two methods has been controversial. Recent development of high spatial and temporal resolution blood vessel wall edge-detection and wall-tracking methods with CDUS increased the accuracy and reliability of blood vessel diameter, hence cerebral blood flow measurement. The aim of this study was to compare the improved CDUS method with 3 T PC-MRI for cerebral blood flow measurements. We found that cerebral blood flow velocity measured in the ICA was lower using PC-MRI than CDUS (left ICA: PC-MRI, 18.0 ± 4.2 vs. CDUS, 25.6 ± 8.6 cm/s; right ICA: PC-MRI, 18.5 ± 4.8 vs. CDUS, 26.6 ± 6.7 cm/s, both p < 0.01). However, ICA diameters measured using PC-MRI were larger (left ICA: PC-MRI, 4.7 ± 0.50 vs. CDUS, 4.1 ± 0.46 mm; right ICA: PC-MRI, 4.5 ± 0.49 vs. CDUS, 4.0 ± 0.45 mm, both p < 0.01). Cerebral blood flow velocity measured in the left vertebral artery with PC-MRI was also lower than CDUS, but no differences in vertebral artery diameter were observed between the methods. Dynamic changes and/or intrinsic physiological fluctuations may have caused these differences in vessel diameter and velocity measurements between the methods. However, estimation of volumetric cerebral blood flow was similar and correlated between the methods despite the presence of large individual differences. These findings support the use of CDUS for cerebral blood flow measurements in the ICA and vertebral artery.

Perfusion Deficits and Functional Connectivity Alterations in Memory-Related Regions of Patients with Post-Traumatic Stress Disorder.

To explore the potential alterations in cerebral blood flow (CBF) and functional connectivity of recent onset post-traumatic stress disorder (PTSD) induced by a single prolonged trauma exposure, we recruited 20 survivors experiencing the same coal mining flood disaster as the PTSD (n = 10) and non-PTSD (n = 10) group, respectively. The pulsed arterial spin labeling (ASL) images were acquired with a 3.0T MRI scanner and the partial volume (PV) effect in the images was corrected for better CBF estimation. Alterations in CBF were analyzed using both uncorrected and PV-corrected CBF maps. By using altered CBF regions as regions-of-interest, seed-based functional connectivity analysis was then performed. While only one CBF deficit in right corpus callosum of PTSD patients was detected using uncorrected CBF, three more regions (bilateral frontal lobes and right superior frontal gyrus) were identified using PV-corrected CBF. Furthermore, the regional CBF of right superior frontal gyrus exhibited significantly negative correlation with the symptom severity (r = −0.759, p = 0.018). The resting-state functional connectivity analysis revealed increased connectivity between left frontal lobe and right parietal lobe. The results indicated the symptom-specific perfusion deficits and an aberrant connectivity in memory-related regions of PTSD patients when using PV-corrected ASL data. It also suggested that PV-corrected CBF exhibits more subtle changes that may be beneficial to perfusion and connectivity analysis.

Comparison of non-invasive MRI measurements of cerebral blood flow in a large multisite cohort

Arterial spin labeling and phase contrast magnetic resonance imaging provide independent non-invasive methods for measuring cerebral blood flow. We compared global cerebral blood flow measurements obtained using pseudo-continuous arterial spin labeling and phase contrast in 436 middle-aged subjects acquired at two sites in the NHLBI CARDIA multisite study. Cerebral blood flow measured by phase contrast (CBFPC: 55.76 ± 12.05 ml/100 g/min) was systematically higher (p < 0.001) and more variable than cerebral blood flow measured by pseudo-continuous arterial spin labeling (CBFPCASL: 47.70 ± 9.75). The correlation between global cerebral blood flow values obtained from the two modalities was 0.59 (p < 0.001), explaining less than half of the observed variance in cerebral blood flow estimates. Well-established correlations of global cerebral blood flow with age and sex were similarly observed in both CBFPCASL and CBFPC. CBFPC also demonstrated statistically significant site differences, whereas no such differences were observed in CBFPCASL. No consistent velocity-dependent effects on pseudo-continuous arterial spin labeling were observed, suggesting that pseudo-continuous labeling efficiency does not vary substantially across typical adult carotid and vertebral velocities, as has previously been suggested. Conclusions: Although CBFPCASL and CBFPC values show substantial similarity across the entire cohort, these data do not support calibration of CBFPCASL using CBFPC in individual subjects. The wide-ranging cerebral blood flow values obtained by both methods suggest that cerebral blood flow values are highly variable in the general population.

Impact of tissue T1 on perfusion measurement with arterial spin labeling.

Arterial spin labeling (ASL) may provide quantitative maps of cerebral blood flow (CBF). Because labeled water exchanges with tissue water, this study evaluates the influence of tissue T1 on CBF quantification using ASL. To locally modify T1 , a low dose of manganese (Mn) was intracerebrally injected in one hemisphere of 19 rats (cortex or striatum). Tissue T1 and CBF were mapped using inversion recovery and continuous ASL experiments at 4.7T. Mn reduced the tissue T1 by more than 30% but had little impact on other tissue properties as assessed via dynamic susceptibility and diffusion MRI. Using a single-compartment model, the use of a single tissue T1 value yielded a mean relative ipsilateral (Mn-injected) to contralateral (noninjected) CBF difference of -34% in cortex and -22% in striatum tissue. With a T1 map, these values became -7% and +8%, respectively. A low dose of Mn reduces the tissue T1 without modifying CBF. Heterogeneous T1 impacts the ASL estimate of CBF in a region-dependent way. In animals, and when T1 modifications exceed the accuracy with which the tissue T1 can be determined, an estimate of tissue T1 should be obtained when quantifying CBF with an ASL technique. Magn Reson Med 77:1656-1664, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

INVOSによる継続的脳血流モニタリングが頚動脈内膜剝離術後の過灌流症候群の予測に有用であった1例

Noninvasive monitoring of regional cerebral oxygen saturation (rSO2) has been introduced in settings for estimation of cerebral perfusion and cerebral blood flow. We predicted the risk of cerebral hyperperfusion syndrome following carotid endarterectomy (CEA) by rSO2 monitoring using INVOSTM. A 77-year-old woman with asymptomatic right internal carotid artery (ICA) stenosis was admitted to our hospital and underwent CEA with INVOS monitoring. INVOS value was 70 in the right ICA and 66 in the left ICA before ICA clamping, and 59 and 79, respectively, after ICA clamping. Immediately after declamping, INVOS value was 82 in the right and 71 in the left ICA. As increase in the INVOS value of the right ICA suggested cerebral hyperperfusion, blood pressure was controlled strictly under anesthesia with propofol. Mean flow velocity ratio in the middle cerebral artery (MFV ratio) on the day after the operation was 1.81, and SPECT showed cerebral hyperperfusion in the ipsilateral cerebral hemisphere. Continuous monitoring of rSO2 using INVOS enabled estimation of the risk of cerebral hyperperfusion syndrome. MFV ratio decreased to 1.35 five days after surgery, and the patient awakened from anesthesia. This patient was able to avoid the risk of cerebral hyperperfusion syndrome. In conclusion, INVOS was useful for monitoring hyperperfusion syndrome following CEA.

Hemodynamic Parameter Estimation From Magnetic Resonance Perfusion Imaging With the Tikhonov Regularization Method

In the brain, T2-weighted dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) enables the measurements of hemodynamic parameters, such as cerebral blood flow (CBF) and cerebral blood volume. Accurately characterizing the tissue residue function in DSC-MRI is of crucial importance to the quantification of cerebral hemodynamics. The estimation of the tissue residue function is an inverse problem, and one of the approaches is through the deconvolution. In this paper, Tikhonov regularization is used to reconstruct the residue function with smooth constraints. The influences of pertinent factors, such as signal-to-noise ratio (SNR) and tracer delay on the reconstruction, are analyzed in detail. The simulation results show that the SNR and the tracer delay have little influence on the estimation of CBF. Therefore, the Tikhonov regularization method can accurately estimate the CBF with confidence.

Rapid 3D dynamic arterial spin labeling with a sparse model-based image reconstruction

Dynamic arterial spin labeling (ASL) MRI measures the perfusion bolus at multiple observation times and yields accurate estimates of cerebral blood flow in the presence of variations in arterial transit time. ASL has intrinsically low signal-to-noise ratio (SNR) and is sensitive to motion, so that extensive signal averaging is typically required, leading to long scan times for dynamic ASL. The goal of this study was to develop an accelerated dynamic ASL method with improved SNR and robustness to motion using a model-based image reconstruction that exploits the inherent sparsity of dynamic ASL data. The first component of this method is a single-shot 3D turbo spin echo spiral pulse sequence accelerated using a combination of parallel imaging and compressed sensing. This pulse sequence was then incorporated into a dynamic pseudo continuous ASL acquisition acquired at multiple observation times, and the resulting images were jointly reconstructed enforcing a model of potential perfusion time courses. Performance of the technique was verified using a numerical phantom and it was validated on normal volunteers on a 3-Tesla scanner. In simulation, a spatial sparsity constraint improved SNR and reduced estimation errors. Combined with a model-based sparsity constraint, the proposed method further improved SNR, reduced estimation error and suppressed motion artifacts. Experimentally, the proposed method resulted in significant improvements, with scan times as short as 20s per time point. These results suggest that the model-based image reconstruction enables rapid dynamic ASL with improved accuracy and robustness.

Multi-TI Arterial Spin Labeling MRI with Variable TR and Bolus Duration for Cerebral Blood Flow and Arterial Transit Time Mapping.

Arterial spin labeling (ASL) is an MRI perfusion imaging method from which quantitative cerebral blood flow (CBF) can be calculated. We present a multi-TI ASL method (multi-TI integrated ASL) in which variable post-labeling delays and variable TRs are used to improve the estimation of arterial transit time (ATT) and CBF while shortening the scan time by 41% compared to the conventional methods. Variable bolus widths allow for T1 and M0 estimation from raw ASL data. Multi-TI integrated pseudo-continuous ASL images were collected at 7 TI times ranging 100-4300 ms. Voxel-wise T1 and M0 maps were estimated, then CBF and ATT maps were created using the estimated T1 tissue map. All maps were consistent with physiological values reported in the literature. Based on simulations and in vivo comparisons, this method demonstrates higher CBF and ATT estimation efficiency than other ATT acquisition methods and better fit to the perfusion model. It produces CBF maps with reduced sensitivity to errors from ATT and tissue T1 variations. The estimated M0, T1, and ATT maps also have potential clinical utility. The method requires a single scan acquired within a clinically acceptable scan time (under 6 minutes) and with low sensitivity to motion.

New Regression Equation for 123I-IMP Non-invasive Cerebral Blood Flow Measurement Using the Graph Plot Method.

A graph plot (GP) method using 123I-N-isopropyl-p-iodoamphetamine (123I-IMP) has been proposed as a simple and non-invasive estimation of quantitative cerebral bloodflow (CBF). A regression equation for the GP method was estimated by the data of resting state. Therefore, the accuracy of CBF values in high flow range may be an underestimated possibility in this method.The aim of this study was to formulate a new regression equation for the GP method by the data of resting state and acetazolamide (ACZ) challenge, and to clarify the accuracy of it. The images of 26 consecutive patients who underwent both 123I-IMP chest radioisotope-angiography (RIA) and single photon emission computed tomography (SPECT) examinations were used to construct the new regression equation. Examinations of the resting state and ACZ challenge were performed in different days. All patients were analyzed by both the GP method and autoradiography (ARG) method which is the conventional examination with the one-point arterial blood sampling. A linear regression equation between the index of the input function was obtained by the GP method and CBF value of ARG. The linear regression equation based on the resting data was compared with the equation based on the resting and ACZ challenge (rest+stress) data. Goodliner correlation was obtained between the index of the input function obtained by the GP method and CBF value of the ARG method in the rest+stress state (y=2.75x+15.1, r=0.78). In contrast, correlation results between the index of the input function obtained by the GP method and CBF value of the ARG method in the resting state was expressed as y=2.28x+18.4, r=0.54 rCBF values based on the resting data was 20% underestimated in the high flow range compared with values based on the rest+stress data. The new linear regression equation for the GP method is useful for clinical study. Key words: non-invasive cerebral blood flow measurement method, graph plot (GP), autoradiography (ARG), 123I-N-isopropyl-p-iodoamphetamine (123I-IMP).