Pattern Of Hypoperfusion Research Articles

Transcranial Doppler sonography follow-up study in mild vascular cognitive impairment.

To date, few data to transcranial Doppler sonography (TCD) are available in patients with mild vascular cognitive impairment (VCI) at risk for vascular or mixed dementia. In a previous study in patients with mild VCI and cerebral small vessels disease, a hemodynamic pattern of cerebral hypoperfusion and enhanced vascular resistance were observed; however, longitudinal data are currently lacking. Here, we perform a clinical, psychopathological, and neurosonological follow-up of patients with VCI in order to monitor any progression and to identify TCD measures to detect it. From the original cohort of 161 patients, 127 with VCI (mean age 73.6 ± 7.1; 67 males) were re-evaluated after 5.0 ± 1.8 years. Namely, the Montreal Cognitive Assessment (MoCA), the 17-items Hamilton Depression Rating Scale (HDRS), and the Stroop Color-Word Interference Test (StroopT) were administered to screen for global cognitive status, to quantify depressive symptoms, and to explore executive functions, respectively. Mean blood flow velocity (MBFV), peak systolic blood flow velocity (PSV), end-diastolic blood flow velocity (EDV), pulsatility index (PI), and resistivity index (RI) were recorded from the middle cerebral artery, bilaterally. At follow up, patients exhibited a significant worsening of both MoCA (21.7 ± 2.1 vs. 20.7 ± 2.0) and StroopT scores (57.4 ± 19.4 vs. 59.7 ± 18.6), whereas HDRS showed an improvement, although the mean raw score remained above the cut-off value for depression (10.3 ± 6.6 vs. 9.8 ± 6.3). MBFV, PSV, and EDV showed a significant increase in PSV and PI and a reduction in EDV. When focused to younger patients (<65 years), we confirmed the significant worsening of both MoCA and StroopT but not HDRS, as well as the significant changes in PI and RI. Finally, considering the differences (D) between baseline and follow-up, the following significant correlations emerged, although with a small-to-medium effect size for all of them: positive correlation between MBFV-D and MoCA-D and between RI-D and STROOP-D, and a negative significant correlation between RI-D and MoCA-D. Notwithstanding some limitations, such as the lack of a control group and neuroimaging data at follow-up, TCD may contribute to the early detection, monitoring, and management of VCI patients at risk for dementia. Together with compatible clinical and cognitive features, the exploration of early TCD markers that possibly indicate a higher risk of progression might represent an intriguing research direction and a significant clinical perspective.

Regional cerebral blood flow reflects both neurodegeneration and microvascular integrity across the Alzheimer's continuum.

Alzheimer's disease (AD) typically involves both neurodegenerative and vascular pathologies, each associated with reductions in cerebral blood flow (CBF). However, it remains unclear whether vascular and neural contributions to regional CBF can be differentiated. Using 3D background-suppressed arterial spin labeled perfusion magnetic resonance imaging, we evaluated regional CBF in a cohort of 257 participants across the AD continuum and assessed the impact of risk factors for both AD and small vessel disease (SVD) on regional CBF. Vascular risk factors (VRFs) were associated with reduced CBF in normal-appearing periventricular white matter, while amyloid positivity was associated with reduced CBF in the posterior cingulate cortex and precuneus. Putative SVD-sensitive regions in white matter exhibited diagnosis-related CBF changes comparable to those in typical AD cortical regions. Spatial patterns of hypoperfusion may differentiate AD and VRF-related effects on regional CBF. Our findings also support the contribution of SVD in AD pathogenesis. We used 3D background-suppressed pCASL MRI to evaluate CBF across the AD continuum. Putative SVD-sensitive regions in white matter exhibited diagnosis-related CBF changes. AD and/or SVD risk correlated with reduced CBF in AD and/or SVD-related regions. VRFs were associated with more widespread CBF reductions than amyloid positivity. Spatial patterns of hypoperfusion may differentiate AD and VRF-related effects.

Early phase Amyloid‐PET reproduces metabolic signatures of cognitive decline in Parkinson's disease

AbstractBackgroundEstablishing practical and effective diagnostic pathways for people with cognitive impairment is a crucial international research priority. Traditional (late‐phase) analysis of an amyloid‐beta (Aβ) PET scan (∼90 minutes after radiotracer injection) provides important information about the presence/absence of underlying Alzheimer’s pathology, but no information about brain metabolism/perfusion. Recent work suggests that amyloid‐beta PET tracer uptake shortly after injection (‘early‐phase’) closely reflects brain metabolism and perfusion. Parkinson’s disease (PD), the second most common neurodegenerative disease worldwide, serves as a model disorder in which cognitive impairment occurs across a spectrum, is not specifically associated with underlying brain amyloid status, and has known patterns of altered metabolism and perfusion associated with cognitive decline. We investigated the utility of early‐phase 18F‐Florbetaben Aβ PET (eFBB) uptake as a surrogate marker of cerebral perfusion/metabolism in people with PD. We hypothesised that eFBB uptake would reproduce characteristic patterns of hypometabolism and hypoperfusion associated with cognitive decline in PD, irrespective of late‐phase Aβ status, and positively correlate with a direct measure of cerebral perfusion – ASL MRI.Method115 closely phenotyped PD patients across the spectrum of cognitive impairment underwent dual‐phase (early and late) Aβ PET, structural and perfusion (ASL) MRI, and neuropsychological assessments. Multiple linear regression models compared eFBB uptake with 1) cognitive performance and 2) ASL‐MRI perfusion, correcting for multiple comparisons by family‐wise error correction (threshold‐free cluster enhancement).ResulteFBB uptake significantly correlated with cerebral perfusion across widespread cortical and subcortical regions (r = 0.15‐0.49, p &lt; 0.005, Figure 2). Reduced eFBB uptake was significantly associated with poorer cognitive performance in brain regions previously linked to hypometabolism‐associated cognitive decline in PD: parieto‐occipital regions, middle and inferior temporal gyri, prefrontal cortex and the thalamus (all p &lt; 0.05, Figure 1). These findings were independent of amyloid status.ConclusioneFBB uptake is a reliable surrogate measure for cerebral perfusion/metabolism in a predominantly Aβ negative group. It provides complimentary information to the late‐phase Aβ scan, and can add value whether the late phase is positive or negative. Such dual‐phase PET imaging approaches show significant promise in streamlining diagnostic pathways for people with cognitive impairment.

Regional cerebral blood flow in behavioral variant of FTD: hypoperfusion patterns and clinical associations.

Findings from functional neuroimaging techniques, such as single-photon emission computed tomography (SPECT), may add useful evidence improving Frontotemporal Dementia (FTD) diagnosis. The aim of the present study was to investigate patterns of hypoperfusion in a group of patients diagnosed with the behavioral variant of FTD (bvFTD) and to explore the relationship between brain perfusion and clinical characteristics. Brain perfusion of 23 bvFTD patients was measured with SPECT scintigraphy in lobes and Brodmann areas (BAs) and the NeurogamTM software was used for image analysis. To assess behavioral disturbances and dementia severity, patients' informants completed the Frontotempotal Behavioral Inventory and the Frontotemporal Dementia Rating Scale. Descriptive statistics were used for the detection of pathological hypoperfusion in lobes and selected BAs. Associations among patients' clinical characteristics and perfusion in lobes were explored via non-parametric correlations. Participants presented pathological hypoperfusion in frontal, limbic and temporal lobes. The most prominent deficit was observed in limbic lobes, where all participants showed pathological hypoperfusion. Decreased perfusion was also observed in limbic, frontal and temporal BAs. Perfusion in the left and right frontal lobe was associated with behavioral disturbances and disease severity, which was also correlated with perfusion in right limbic, left and right temporal areas. Patterns of limbic, frontal and temporal hypopefusion were reported in the present study, along with associations between brain perfusion, behavioral disturbance and severity of dementia. Perfusion patterns can help to understand further associated brain biomarkers, contributing to early diagnosis and intervention in bvFTD.

Longitudinal cerebral perfusion in presymptomatic genetic frontotemporal dementia: GENFI results

Effective longitudinal biomarkers that track disease progression are needed to characterize the presymptomatic phase of genetic frontotemporal dementia (FTD). We investigate the utility of cerebral perfusion as one such biomarker in presymptomatic FTD mutation carriers. We investigated longitudinal profiles of cerebral perfusion using arterial spin labeling magnetic resonance imaging in 42 C9orf72, 70 GRN, and 31 MAPT presymptomatic carriers and 158 non-carrier controls. Linear mixed effects models assessed perfusion up to 5 years after baseline assessment. Perfusion decline was evident in all three presymptomatic groups in global gray matter. Each group also featured its own regional pattern of hypoperfusion over time, with the left thalamus common to all groups. Frontal lobe regions featured lower perfusion in those who symptomatically converted versus asymptomatic carriers past their expected age of disease onset. Cerebral perfusion is a potential biomarker for assessing genetic FTD and its genetic subgroups prior to symptom onset. Gray matter perfusion declines in at-risk genetic frontotemporal dementia (FTD). Regional perfusion decline differs between at-risk genetic FTD subgroups . Hypoperfusion in the left thalamus is common across all presymptomatic groups. Converters exhibit greater right frontal hypoperfusion than non-converters past their expected conversion date. Cerebral hypoperfusion is a potential early biomarker of genetic FTD.

Decreased Cerebral Perfusion in Chronic Migraine: A Voxel-based Cerebral Blood Flow Analysis Using 3D Pseudo-continuous Arterial Spin Labeling.

A contrast agent-free approach would be preferable to the frequently used invasive approaches for evaluating cerebral perfusion in chronic migraineurs (CM). In this work, non-invasive quantitative volumetric perfusion imaging was used to evaluate alterations in cerebral perfusion in CM. We used conventional brain structural imaging sequences and 3D pseudo-continuous arterial spin labeling (3D PCASL) to examine thirteen CM patients and fifteen normal controls (NCs). The entire brain gray matter underwent voxel-based analysis, and the cerebral blood flow (CBF) values of the altered positive areas were retrieved to look into the clinical variables' significant correlation. Brain regions with the decreased perfusion were located in the left postcentral gyrus, bilateral middle frontal gyrus, left middle occipital gyrus, left superior parietal lobule, left medial segment of superior frontal gyrus, and right orbital part of the inferior frontal gyrus. White matter fibers with decreased perfusion were located in bilateral superior longitudinal tracts, superior corona radiata, external capsules, anterior and posterior limbs of the internal capsule, anterior corona radiata, inferior longitudinal fasciculus, and right corticospinal tract. However, the correlation analysis showed no significant correlation between the CBF value of the above positive brain regions with clinical variables (p > 0.05). The current study provided more useful information to comprehend the pathophysiology of CM and revealed a new insight into the neural mechanism of CM from the pattern of cerebral hypoperfusion.

Early-phase amyloid PET reproduces metabolic signatures of cognitive decline in Parkinson's disease.

Recent work suggests that amyloid beta (Aβ) positron emission tomography (PET) tracer uptake shortly after injection ("early phase") reflects brain metabolism and perfusion. We assessed this modality in a predominantly amyloid-negative neurodegenerative condition, Parkinson's disease (PD), and hypothesized that early-phase 18F-florbetaben (eFBB) uptake would reproduce characteristic hypometabolism and hypoperfusion patterns associated with cognitive decline in PD. One hundred fifteen PD patients across the spectrum of cognitive impairment underwent dual-phase Aβ PET, structural and arterial spin labeling (ASL) magnetic resonance imaging (MRI), and neuropsychological assessments. Multiple linear regression models compared eFBB uptake to cognitive performance and ASL MRI perfusion. Reduced eFBB uptake was associated with cognitive performance in brain regions previously linked to hypometabolism-associated cognitive decline in PD, independent of amyloid status. Furthermore, eFBB uptake correlated with cerebral perfusion across widespread regions. EFBB uptake is a potential surrogate measure for cerebral perfusion/metabolism. A dual-phase PET imaging approach may serve as a clinical tool for assessing cognitive impairment. Images taken at amyloid beta (Aβ) positron emission tomography tracer injection may reflect brain perfusion and metabolism.Parkinson's disease (PD) is a predominantly amyloid-negative condition.Early-phase florbetaben (eFBB) in PD was associated with cognitive performance.eFBB uptake reflects hypometabolism-related cognitive decline in PD.eFBB correlated with arterial spin labeling magnetic resonance imaging measured cerebral perfusion.eFBB distinguished dementia from normal cognition and mild cognitive impairment.Findings were independent of late-phase Aβ burden.Thus, eFBB may serve as a surrogate measure for brain metabolism/perfusion.

Patterns of regional cerebral hypoperfusion in early Parkinson's disease: Clinical implications

IntroductionThis study aimed to investigate whether regional cerebral perfusion patterns on early-phase 18F-FP-CIT PET scans, which is typically coupled to cerebral metabolism, predict the long-term prognosis of Parkinson's disease (PD). MethodsWe enrolled 397 drug-naïve patients with early-stage PD who underwent dual-phase 18F-FP-CIT PET scans. After quantifying the early-phase 18F-FP-CIT PET images, cluster analysis was performed to delineate the PD subtypes according to the patterns of regional cerebral perfusion. We compared the risk of developing levodopa-induced dyskinesia (LID), wearing-off, freezing of gait (FOG), and dementia between the PD subtypes. ResultsCluster analysis classified patients into three subtypes: cluster 1 (relatively preserved cortical uptake; n = 175), cluster 2 (decreased uptake in the frontal, parietal, and temporal regions; n = 151), and cluster 3 (decreased uptake in more extensive regions, additionally involving the lateral occipital regions; n = 71). Cluster 1 was characterized by a younger age-of-onset, less severe motor deficits, less severely decreased 18F-FP-CIT binding in the caudate, and better cognitive performance. Cluster 3 was characterized by an older age-of-onset, more severe motor deficits, and poorer cognitive performance. Cluster 2 was intermediate between clusters 1 and 3. Cox regression analyses demonstrated that clusters 2 and 3 had a higher risk for dementia conversion than cluster 1, whereas the risk for developing LID, wearing-off, and FOG did not differ among the clusters. ConclusionThe patterns of regional cerebral perfusion can provide information on long-term prognosis with regards to cognitive, but not motor aspects of patients with early-stage PD.

The Role of Dual-Phase 18 F-FP-CIT PET to Early Diagnosis of Corticobasal Syndrome.

Corticobasal syndrome (CBS) is a neurodegeneration characterized by asymmetric parkinsonism, dystonia, myoclonus, and apraxia. In the early stage, CBS presents with asymmetric parkinsonism and cortical symptoms (apraxia and alien hand), and neuroimaging finding is often vague, making early clinical differentiation from idiopathic Parkinson disease (IPD) challenging. This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter (DAT) uptake using dual-phase FP-CIT PET in discriminating between CBS and IPD at early stage. The study enrolled clinically diagnosed CBS (n = 11) and IPD (n = 22) patients (age and sex matched). All participants underwent dual-phase 18 F-FP-CIT PET, and regional SUV ratio (SUVR) was obtained by semiquantitative analysis. The early perfusion imaging and DAT imaging were compared between groups. The regional SUVRs (early phase) of the frontal lobe, thalamus, cingulate, and caudate were significantly lower in patients with CBS, whereas the SUVR of occipital lobe was lower in the IPD group. The CBS group exhibited more prominent asymmetry than the IPD group, particularly in the perirolandic area, superior frontal gyrus, and anterior parietal lobe in early phase PET. Striatal DAT uptake (delayed phase) revealed that the caudate showed lower SUVR and prominent asymmetry in the CBS group, and the caudate-to-putamen ratio (CP ratio) was significantly lower in CBS patients ( P < 0.001). Among the parameters (early and delayed), the CP ratio in DAT exhibited the most powerful discriminative power from receiver operating characteristic curve comparison (area under curve = 0.983). This study demonstrated that the dual-phase FP-CIT PET is useful in differentiating CBS and IPD in the early stage of the disease, and a lower CP ratio of DAT imaging is highly informative for distinguishing between corticobasal degeneration and IPD.

Early‐phases [18F]florbetapir and [18F]flutemetamol images as proxies of brain metabolism in the Alzheimer’s disease spectrum

AbstractBackgroundAlzheimer’s disease (AD) neuropathologic changes are β‐amyloid (Aβ) deposition, pathologic tau, and neurodegeneration. Dual‐phase amyloid‐PET might be able to evaluate Aβ deposition and neurodegeneration with a single tracer injection. Early‐frames of amyloid‐PET scans provide a proxy for cerebral perfusion, which has shown good correlations with neural dysfunction measured through metabolic consumption, while the late‐frames depict amyloid distribution. Our study aims to assess the comparability between early frames of amyloid‐PET scans and [18F]fluorodeoxyglucose (FDG) PET in their topography and their ability to discriminate patients in the AD continuum.Method166 subjects evaluated at the Geneva Memory Center (Cognitively Unimpaired, CU = 61; Mild Cognitive Impairment, MCI = 73; Dementia = 21) underwent early‐phase amyloid‐PET – using either [18F]florbetapir (eFBP) (n = 95) or [18F]flutemetamol (eFMM) (n = 72) – and FDG PET. Standardized uptake value ratios (SUVR) were extracted within key regions sensitive for AD (metaROI) to evaluate the correlation of eFBP/eFMM and their respective FDG PET scans. To compare the discriminative power of eFBP, eFMM, and FDG SUVR between Aβ‐negative CU and Aβ‐positive impaired patients, receiver operating characteristic analyses and voxel‐wise t‐tests were performed. SPM single‐subject procedure was applied to investigate hypometabolic and hypoperfusion maps and their spatial overlap by means of DICE.ResultStrong positive correlations were found between eFBP/eFMM and FDG SUVR independently of Aβ status and Aβ radiotracers (r&gt;0.85, p&lt;0.001). Both eFBP and eFMM, and FDG SUVR significantly discriminated AD cognitively impaired patients from CU in the metaROI (AUCFBP = 0.768; AUCFMM = 0.778), with FDG performing slightly better than others (AUCFDG = 0.797). For all tracers, voxel‐wise analyses confirmed reduced signals in regions typically belonging to AD hypometabolic pattern in AD patients when compared to controls. SPM single‐subject analysis revealed different hypometabolism and hypoperfusion patterns with a high spatial concordance, differing between stages (DICE average: AD dementia = 0.91; Aβ‐positive MCI = 0.61).ConclusionDistribution of perfusion was comparable to that of metabolism at group level and at single‐subject level. Our findings indicate that eFBP and eFMM imaging provide information closely related to brain regional glucose metabolism supporting their use for individual classification in clinical practice.

Differentiation of Alzheimer's Disease from Frontotemporal Dementia and Mild Cognitive Impairment Based on Arterial Spin Labeling Magnetic Resonance Imaging: A Pilot Cross-Sectional Study from PUMCH Dementia Cohort.

Arterial spin labeling (ASL) is helpful in early diagnosis and differential diagnosis of Alzheimer's disease (AD), with advantages including no exposure to radioactivity, no injection of a contrast agent, more accessible, and relatively less expensive. To establish the perfusion pattern of different dementia in Chinese population and evaluate the effectiveness of ASL in differentiating AD from cognitive unimpaired (CU), mild cognitive impairment (MCI), and frontotemporal dementia (FTD). Four groups of participants were enrolled, including AD, FTD, MCI, and CU based on clinical diagnosis from PUMCH dementia cohort. ASL image was collected using 3D spiral fast spin echo-based pseudo-continuous ASL pulse sequence with background suppression and a high resolution T1-weighted scan covering the whole brain. Data processing was performed using Dr. Brain Platform to get cerebral blood flow (ml/100g/min) in every region of interest cortices. Participants included 66 AD, 26 FTD, 21 MCI, and 21 CU. Statistically, widespread hypoperfusion neocortices, most significantly in temporal-parietal-occipital cortices, but not hippocampus and subcortical nucleus were found in AD. Hypoperfusion in parietal lobe was most significantly associated with cognitive decline in AD. Hypoperfusion in parietal lobe was found in MCI and extended to adjacent temporal, occipital and posterior cingulate cortices in AD. Significant reduced perfusion in frontal and temporal cortices, including subcortical nucleus and anterior cingulate cortex were found in FTD. Hypoperfusion regions were relatively symmetrical in AD and left predominant especially in FTD. Specific patterns of ASL hypoperfusion were helpful in differentiating AD from CU, MCI, and FTD.

Arterial spin labelling reveals multi-regional cerebral hypoperfusion in patients with transient ischemic attack that are unrelated to ischemia location: A proof-of-concept study

Patients with transient ischemic attack (TIA) have a substantially increased risk of early dementia. In this exploratory study, we aim to determine whether patients with TIA have 1) measurable regional cerebral hypoperfusion unrelated to the location of ischemia, and 2) determine the relationship of regional cerebral blood flow (rCBF) with their cognitive profiles. Patients with TIA (N=49) and seventy-nine (N=79) age and sex matched controls underwent formal neuropsychological testing and MRI. Quantitative arterial spin labelling rCBF maps (mL/min/100g) were registered to the corresponding high resolution T1-weighted image. Linear regression was used to determine the association between demographic, clinical and cognitive variables and rCBF. Patients with TIA had significantly (p<0.05) lower cognitive scores in the MMSE, MOCA, ACE-R, WAIS-IV DS Coding and Trail Making Tests A and B compared to controls. TIA patients had significantly lower rCBF in the left entorhinal cortex (p=0.03), right posterior cingulate (p=0.04), and right precuneus (p=0.05), after adjusting for age and sex, that were unrelated to the regional anatomical volume and DWI positivity. Regional hypoperfusion in the right posterior cingulate and right precuneus was associated with impaired visual memory (BVMT total, p=0.05 for both regions) and slower processing speed (TMT A, p=0.04 and p=0.01), respectively after adjusting for age and sex. TIA patients have patterns of regional hypoperfusion in multiple cortical regions unrelated to the parcellated regional anatomical volume or the presence of a DWI lesion. Regional hypoperfusion in patients with TIA may be an early marker conferring risk of future cognitive decline that needs to be confirmed by future studies.

Dual-phase 18 F-FP-CIT positron emission tomography and cardiac 123 I-MIBG scintigraphy of Parkinson's disease patients with GBA mutations: evidence of the body-first type?

Parkinson's disease (PD) with glucocerebrosidase (GBA) gene mutation (GBA-PD) is known to show more rapid clinical progression than sporadic PD without GBA mutation (sPD). This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter uptake and cardiac meta-iodobenzylguanidine (MIBG) uptake of GBA-PD in comparison to sPD. Through next-generation sequencing analysis targeting 41 genes, a total of 16 GBA-PD and 24 sPD patients (sex, age matched) were enrolled in the study, and the clinical, dual-phase [18 F]-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (1 8 F-FP-CIT) positron emission tomography (PET)and cardiac 123 I-MIBG scintigraphy results were compared between the two groups. The GBA-PD group had higher rates of rapid eye movement sleep behavior disorder, orthostatic hypotension and neuropsychiatric symptoms than the sPD group. Early-phase 18 F-FP-CIT PETshowed significantly lower standard uptake value ratio on bilateral posterior parietal cortex (0.94 ± 0.05 vs. 1.02 ± 0.04, p=0.011) and part of the occipital cortex (p < 0.05) in the GBA-PD group than the sPD group. In striatal dopamine transporter uptake, the regional standard uptake value ratio, asymmetry index and caudate-to-putamen ratio were similar between the two groups. The GBA-PD group had a lower heart-to-mediastinum uptake ratio in 123 I-MIBG scintigraphy than the sPD group. The GBA-PD patients showed decreased regional perfusion in the bilateral posterior parietal and occipital cortex. Cardiac sympathetic denervation and non-motor symptoms (orthostatic hypotension, rapid eye movement sleep behavior disorder) were more common in GBA-PD than sPD. These findings suggest that GBA-PD patients have more widespread peripheral (extranigral) α-synuclein accumulation, representing a body-first PD subtype.

Venous Outflow and Parenchymal Hemorrhage: A Clogged Drain Problem?

Venous Outflow and Parenchymal Hemorrhage: A Clogged Drain Problem?

Pulsatile Ocular Blood Flow Registered with Optical Coherence Tomography Angiography in Patients with High Intraocular Pressure.

To present a series of cases demonstrating pulsatile ocular blood flow registered with optical coherence tomography angiography (OCTA) and to describe the clinical characteristics of this phenomenon. Seven primary open-angle glaucoma patients (eight eyes) were included, with a median age of 67.0 years (range, 39-73 years), who demonstrated alternating hypointense bands of OCTA flow signal on the macular scan at increased intraocular pressure (IOP). All patients received comprehensive ophthalmic examination, OCTA examination with RTVue-XR, and infrared video scanning laser ophthalmoscopy. Changes in retinal microcirculation were assessed on the raw OCTA scans as well as the resultant vessel density maps before and after IOP reduction. Median IOP in study eyes was 39.0 mmHg (range, 36-58 mmHg). Hypointense bands of OCTA flow signal were associated with arterial pulsation on video scanning laser ophthalmoscopy in all eyes and agreed with the heart rate and resulted in a spotted grid pattern of hypoperfusion on vessel density maps in seven eyes. Median vessel density in superficial capillary plexus and deep capillary plexus was 32.4% and 47.2%, respectively, at high IOP, and increased statistically significantly to 36.5% (P = 0.016) and 50.9% (P = 0.016), respectively, after IOP reduction. Alternating hypointense flow signal bands on OCTA scans are possibly caused by the pulsatile character of retinal blood flow during the cardiac cycle in eyes with high IOP and may reflect the imbalance between IOP and perfusion pressure. This phenomenon is responsible for the reversible decrease of vessel density at high IOP.

Comparison of dynamic susceptibility contrast enhanced MR and FDG-PET brain studies in patients with Alzheimer’s disease and amnestic mild cognitive impairment

BackgroundThe aim of this study was to compare Dynamic Susceptibility Contrast Enhanced MRI (DSC-MRI) and PET with [18F]flurodeoxyglucose (FDG-PET) in the diagnosis of Alzheimer’s Disease (AD) and amnestic Mild Cognitive Impairment (aMCI).MethodsTwenty-seven age-and sex-matched patients with AD, 39 with aMCI and 16 controls underwent brain DSC-MRI followed by FDG-PET. Values of relative Cerebral Blood Volume (rCBV) and rCBV z-scores from frontal, temporal, parietal and PCG cortices were correlated with the rate of glucose metabolism from PET. Sensitivity, specificity and accuracy of DSC-MRI and FDG-PET in the diagnosis of AD and aMCI were assessed and compared.ResultsIn AD, hypoperfusion was found within all the examined locations, while in aMCI in both parietal and temporal cortices and left PCG. FDG-PET showed the greatest hypometabolism in parietal, temporal and left PCG regions in both AD and aMCI. FDG-PET was more accurate in distinguishing aMCI from the controls than DSC-MRI. In the AD and combined group (AD + aMCI) there were numerous correlations between DSC-MRI and FDG-PET results.ConclusionsIn AD the patterns of hypoperfusion and glucose hypometabolism are similar, thus DSC-MRI may be a competitive method to FDG-PET. FDG-PET is a more accurate method in the diagnosis of aMCI.

Unclassified fluent variants of primary progressive aphasia: distinction from semantic and logopenic variants.

Primary progressive aphasia, a neurodegenerative syndrome, presents mainly with language impairment. Both semantic and logopenic variants are fluent variants of primary progressive aphasia. Before the research criteria of primary progressive aphasia were proposed, progressive fluent aphasias, such as progressive anomic aphasia, transcortical sensory aphasia and Wernicke’s aphasia, were reported as classical progressive fluent aphasias seen in Alzheimer’s disease. However, since the research criteria of primary progressive aphasia were established, classical fluent variants (other than semantic and logopenic variants) have been neglected and have not been included in the current classification of primary progressive aphasia. This study aimed to determine whether unclassified fluent variants (other than semantic and logopenic variants) can be manifestations of primary progressive aphasia. This study also reconfirmed the characteristics of classical progressive fluent aphasia, such as progressive anomic aphasia, progressive transcortical sensory aphasia and progressive Wernicke’s aphasia as unclassified fluent variants of primary progressive aphasia, using comparison with the current model of primary progressive aphasia. Twelve consecutive patients with an unclassified fluent variant other than semantic or logopenic variant underwent language, neurological, neuropsychological and neuroimaging (MRI and single-photon emission computed tomography) testing. Based on comprehensive language tests, we redefined the diagnoses as primary progressive anomic aphasia (n = 8), primary progressive transcortical sensory aphasia (n = 3) and primary progressive Wernicke’s aphasia (n = 1). Anomic aphasia was characterized by anomia but preserved repetition and comprehension; transcortical sensory aphasia by relatively preserved repetition but poor word comprehension; and Wernicke’s aphasia by poor repetition and word comprehension. In patients with anomic aphasia, voxel-based morphometry of MRI data revealed cortical atrophy, which was most prominent in the temporoparietal lobes, with no obvious lateralization; in two-thirds of patients with transcortical sensory aphasia and in one patient with Wernicke’s aphasia, it revealed atrophy, predominantly in the left temporoparietal lobe. Statistical analysis of single-photon emission computed tomography using three-dimensional stereotactic surface projections revealed patterns of left-sided hypoperfusion in the majority of patients. The temporal and parietal lobes were involved in all cases; the degree of hypoperfusion was higher in patients with transcortical sensory aphasia or Wernicke’s aphasia than in patients with anomic aphasia. The present study demonstrated the clinical and imaging features of 12 patients with an unclassified fluent variant of primary progressive aphasia, which we redefined as primary progressive anomic aphasia, primary progressive transcortical sensory aphasia and primary progressive Wernicke’s aphasia. Classical fluent variants other than semantic and logopenic variants can be found in primary progressive aphasia.

Cerebral perfusion in posterior reversible encephalopathy syndrome measured with arterial spin labeling MRI

Background and purposeThe pathophysiologic basis of posterior reversible encephalopathy syndrome (PRES) remains controversial. Hypertension (HTN)-induced autoregulatory failure with subsequent hyperperfusion is the leading hypothesis, whereas alternative theories suggest vasoconstriction-induced hypoperfusion as the underlying mechanism. Studies using contrast-based CT and MR perfusion imaging have yielded contradictory results supporting both ideas. This work represents one of the first applications of arterial spin labeling (ASL) to evaluate cerebral blood flow (CBF) changes in PRES. Materials and methodsAfter obtaining Institutional Review Board approval, MRI reports at our institution from 07/2015 to 09/2020 were retrospectively searched and reviewed for mention of “PRES” and “posterior reversible encephalopathy syndrome.” Of the resulting 103 MRIs (performed on GE 1.5 Tesla or 3 Tesla scanners), 20 MRIs in 18 patients who met the inclusion criteria of clinical and imaging diagnosis of PRES and had diagnostic-quality pseudocontinuous ASL scans were included. Patients with a more likely alternative diagnosis, technically non-diagnostic ASL, or other intracranial abnormalities limiting assessment of underlying PRES features were excluded. Perfusion in FLAIR-affected brain regions was qualitatively assessed using ASL and characterized as hyperperfusion, normal, or hypoperfusion. Additional quantitative analysis was performed by measuring average gray matter CBF in abnormal versus normal brain regions. ResultsHTN was the most common PRES etiology (65%). ASL showed hyperperfusion in 13 cases and normal perfusion in 7 cases. A hypoperfusion pattern was not identified. Quantitative analysis of gray matter CBF among patients with visually apparent hyperperfusion showed statistically higher perfusion in affected versus normal appearing brain regions (median CBF 100.4 ml/100 g-min vs. 61.0 ml/ 100 g-min, p < 0.001). ConclusionElevated ASL CBF was seen in the majority (65%) of patients with PRES, favoring the autoregulatory failure hypothesis as a predominant mechanism. Our data support ASL as a practical way to assess and noninvasively monitor cerebral perfusion in PRES that could potentially alter management strategies.

Concordance of regional hypoperfusion by pCASL MRI and 15O-water PET in frontotemporal dementia: Is pCASL an efficacious alternative?

BackgroundClinical diagnosis of frontotemporal dementia (FTD) remains a challenge due to the overlap of symptoms among FTD subtypes and with other psychiatric disorders. Perfusion imaging by arterial spin labeling (ASL) is a promising non-invasive alternative to established PET techniques; however, its sensitivity to imaging parameters can hinder its ability to detect perfusion abnormalities. PurposeThis study evaluated the similarity of regional hypoperfusion patterns detected by ASL relative to the gold standard for imaging perfusion, PET with radiolabeled water (15O-water). Methods and materialsPerfusion by single-delay pseudo continuous ASL (SD-pCASL), free-lunch Hadamard encoded pCASL (FL_TE-pCASL), and 15O-water data were acquired on a hybrid PET/MR scanner in 13 controls and 9 FTD patients. Cerebral blood flow (CBF) by 15O-water was quantified by a non-invasive approach (PMRFlow). Regional hypoperfusion was determined by comparing individual patients to the control group. This was performed using absolute (aCBF) and CBF normalized to whole-brain perfusion (rCBF). Agreement was assessed based on the fraction of overlapping voxels. Sensitivity and specificity of pCASL was estimated using hypoperfused regions of interest identified by 15O-water. ResultsRegion of interest (ROI) based perfusion measured by 15O-water strongly correlated with SD-pCASL (R = 0.85 ± 0.1) and FL_TE-pCASL (R = 0.81 ± 0.14). Good agreement in terms of regional hypoperfusion patterns was found between 15O-water and SD-pCASL (sensitivity = 70%, specificity = 78%) and between 15O-water and FL_TE-pCASL (sensitivity = 71%, specificity = 73%). However, SD-pCASL showed greater overlap (43.4 ± 21.3%) with 15O-water than FL_TE-pCASL (29.9 ± 21.3%). Although aCBF and rCBF showed no significant differences regarding spatial overlap and metrics of agreement with 15O-water, rCBF showed considerable variability across subtypes, indicating that care must be taken when selecting a reference region. ConclusionsThis study demonstrates the potential of pCASL for assessing regional hypoperfusion related to FTD and supports its use as a cost-effective alternative to PET.

Transient Global Cerebral Hypoperfusion as a Characteristic Cerebral Hemodynamic Pattern in the Acute Stage after Combined Revascularization Surgery for Pediatric Moyamoya Disease: N-Isopropyl-P-[123I] Iodoamphetamine Single-Photon Emission Computed Tomography Study

Introduction: Surgical revascularization prevents cerebral ischemic attack by improving cerebral blood flow (CBF) in both adult and pediatric patients with moyamoya disease (MMD). Uneven hemodynamic changes, including local cerebral hyperperfusion and remote ischemia, can cause delayed intracerebral hemorrhage and perioperative infarctions in adult MMD patients, but the characteristic hemodynamic pattern among pediatric MMD patients after revascularization surgery is poorly understood. Methods: This study included 16 consecutive pediatric MMD patients (age, 6–16 years; mean age, 11.3) undergoing superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-duro-myo-synangiosis on 21 affected hemispheres. Perioperative management was conducted by aspirin administration and strict blood pressure control (110–130 mm Hg). We prospectively performed N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography on postoperative days (POD) 1 and 7 and analyzed the temporal changes in perioperative hemodynamics. Results: Four patients (19.0%, 4/21) exhibited immediate CBF improvement from POD 1, which was classified as “immediate redistribution pattern.” In contrast, 9 (42.9%, 9/21) demonstrated transient hemispheric global hypoperfusion at POD 1 and subsequent CBF improvement at POD 7, which was defined as “transient hypoperfusion pattern.” Although 8 patients, including 4 with “transient hypoperfusion pattern” (44.4, 4/9), developed mild transient neurological deterioration in the acute stage, it resolved in all 21 patients, and there were no permanent neurological deficits. Discussion/Conclusions: This study revealed that the “transient hypoperfusion pattern” after revascularization surgery is relatively common among pediatric MMD patients, and its outcome is favorable under strict perioperative management.