Changes In Brain Perfusion Research Articles

Non-contrast quantitative study of brain perfusion changes in multiple sclerosis

Non-contrast quantitative study of brain perfusion changes in multiple sclerosis

On the Regulation of Arterial Blood Pressure by an Intracranial Baroreceptor

Introduction: There is significant evidence for the existence of an intracranial baroreceptor mechanism(s) capable of sensing physiological changes in cerebral blood flow (Marina et al., 2020). However, little is known about the sensitivity of this mechanism to changes in brain perfusion and its interaction with inputs from the peripheral (arterial) baroreceptors. The aim of this study was to characterise the cardiovascular responses to physiological changes in cerebral perfusion induced by experimental manipulations of intracranial pressure (ICP). Methods: The experiments were performed in adult Sprague-Dawley rats (250–300 g), anesthetized with urethane (induction: 1.3 g kg−1, i.p.; maintenance: 10–25 mg kg−1 h−1, i.v.). The femoral artery and vein were cannulated for measurement of arterial blood pressure (ABP) and administration of anaesthetic. The trachea was cannulated, and the animal was mechanically ventilated. The lateral cerebral ventricles were cannulated and connected via saline-filled catheters to a pressure transducer to record ICP and to a “water column” to allow controlled manipulation of ICP. The experiments included the denervation of the arterial baroceptors, stimulation of the aortic depressor nerve and recording of renal sympathetic nerve activity. Results: The resting ICP in rats anesthetized with urethane was 6.2 ± 0.7 mmHg (n=8). Following a small craniotomy that reduced ICP to 0 mmHg, ABP decreased by 11.2 mmHg (n=6) within 30 min. Restoring the integrity of the intracranial space increased ABP to the baseline level. Progressive increases in ABP were observed in response to experimentally-induced increases in ICP by 5, 10, 15 and 20 mmHg, revealing a linear relationship between ICP and systemic arterial pressure within the physiological range of ICP changes. In the absence of inputs from the arterial baroceptors (bilateral sino-aortic denervation and vagotomy) the ABP responses to ICP increases were preserved. Analysis of the ABP and heart rate responses to the electrical stimulation of the aortic depressor nerve suggested baroreflex re-setting at raised ICP. Renal nerve recordings demonstrated increased sympathetic activity at raised ICP (172 ± 34.91 % at 20 mmHg ICP (p=0.003; n=7) with markedly enhanced bursts of activity during the inspiratory phase of the respiratory cycle. Conclusion: These data demonstrate that the intracranial baroceptor mechanism is highly sensitive to changes in cerebral perfusion within the physiological range and suggest that cerebral blood flow is an important determinant of systemic ABP. The data suggest that at raised ICP the baroreflex control of sympathetic vasomotor activity is reset and provides effective control of arterial blood pressure at a higher level required to compensate for reduced brain perfusion. Marina, N., Christie, I.N., Korsak, A., Doronin, M., Brazhe, A., Hosford, P.S., Wells, J.A., Sheikhbahaei, S., Humoud, I., Paton, J.F. and Lythgoe, M.F., 2020. Astrocytes monitor cerebral perfusion and control systemic circulation to maintain brain blood flow. Nature Communications, 11(1), 131. This PhD Studentship is funded by the British Heart Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Synaptic loss and its association with symptom severity in Parkinson’s disease

Parkinson’s disease (PD) is the fastest growing neurodegenerative disease, but at present there is no cure, nor any disease-modifying treatments. Synaptic biomarkers from in vivo imaging have shown promise in imaging loss of synapses in PD and other neurodegenerative disorders. Here, we provide new clinical insights from a cross-sectional, high-resolution positron emission tomography (PET) study of 30 PD individuals and 30 age- and sex-matched healthy controls (HC) with the radiotracer [11C]UCB-J, which binds to synaptic vesicle glycoprotein 2A (SV2A), and is therefore, a biomarker of synaptic density in the living brain. We also examined a measure of relative brain perfusion from the early part of the same PET scan. Our results provide evidence for synaptic density loss in the substantia nigra that had been previously reported, but also extend this to other early-Braak stage regions known to be affected in PD (brainstem, caudate, olfactory cortex). Importantly, we also found a direct association between synaptic density loss in the nigra and severity of symptoms in patients. A greater extent and wider distribution of synaptic density loss in PD patients with longer illness duration suggests that [11C]UCB-J PET can be used to measure synapse loss with disease progression. We also demonstrate lower brain perfusion in PD vs. HC groups, with a greater extent of abnormalities in those with longer duration of illness, suggesting that [11C]UCB-J PET can simultaneously provide information on changes in brain perfusion. These results implicate synaptic imaging as a useful PD biomarker for future disease-modifying interventions.

Effects of Low-Level Blast on Neurovascular Health and Cerebral Blood Flow: Current Findings and Future Opportunities in Neuroimaging.

Low-level blast (LLB) exposure can lead to alterations in neurological health, cerebral vasculature, and cerebral blood flow (CBF). The development of cognitive issues and behavioral abnormalities after LLB, or subconcussive blast exposure, is insidious due to the lack of acute symptoms. One major hallmark of LLB exposure is the initiation of neurovascular damage followed by the development of neurovascular dysfunction. Preclinical studies of LLB exposure demonstrate impairment to cerebral vasculature and the blood-brain barrier (BBB) at both early and long-term stages following LLB. Neuroimaging techniques, such as arterial spin labeling (ASL) using magnetic resonance imaging (MRI), have been utilized in clinical investigations to understand brain perfusion and CBF changes in response to cumulative LLB exposure. In this review, we summarize neuroimaging techniques that can further our understanding of the underlying mechanisms of blast-related neurotrauma, specifically after LLB. Neuroimaging related to cerebrovascular function can contribute to improved diagnostic and therapeutic strategies for LLB. As these same imaging modalities can capture the effects of LLB exposure in animal models, neuroimaging can serve as a gap-bridging diagnostic tool that permits a more extensive exploration of potential relationships between blast-induced changes in CBF and neurovascular health. Future research directions are suggested, including investigating chronic LLB effects on cerebral perfusion, exploring mechanisms of dysautoregulation after LLB, and measuring cerebrovascular reactivity (CVR) in preclinical LLB models.

Assessing the Role of PLCG2*M28L Risk In A Novel Mouse Model Late‐Onset Alzheimer’s Disease

AbstractBackgroundMODEL‐AD has developed and characterized novel mouse models that aim to better phenocopy human LOAD for preclinical testing. More than 40 different models carrying combinations of LOAD risk factors have been created and assessed for relevance to LOAD. In this study, we aim to determine the mechanisms by which variations in the phospholipase C gamma 2 (PLCG2) gene increase risk for LOAD.MethodsThe M28L variant in PLCG2 (PLCG2*M28L) was prioritized as a LOAD risk factor. Mice were generated by CRISPR/CAS9 introduction of Plcg2*M28L variant on to LOAD1 (B6.APOE4.Trem2*R47H) and transcriptional profiling of brain hemispheres from 12 months old mice was used to evaluate molecular effects of Plcg2*M28L. To evaluate the contribution of Plcg2*M28L to LOAD risk, mice where placed on control or high fat diet (HFD) to serve as an environmental driver of neuroinflammation. Female and male LOAD1.Plcg2*M28L and LOAD1 control mice are being characterized at 4 and 12 mos through the MODEL‐AD phenotyping pipeline, which includes in vivo imaging of brain perfusion and glycolytic metabolism, multi‐omics, fluid biomarkers, cognition, and neuropathology.ResultsLOAD1.Plcg2*M28L mice showed brain transcriptomic alignment at 12 mos to human LOAD, and was prioritized for deep phenotyping. LOAD1 mice on HFD showed significant regional reductions in brain glycolysis and increased perfusion relative to controls yielding an uncoupled phenotype. By contrast, LOAD1.Plcg2*M28L mice showed a little to no regional changes in brain glycolysis or perfusion and few uncoupled regions. Multi‐resolution connectomics revealed a decrease in cluster number and organization in LOAD1 but not LOAD1.Plcg2*M28L for both sexes fed HFD compared with control diets. By 12 mos, male and female LOAD1.Plcg2*M28L mice on HFD showed opposite changes in clustering coefficient, network degree, and network density, with males showing a decrease and females an increase relative to controls. Mice carrying Plcg2*M28L variants are also being phenotyping at 18 and 24 mos.ConclusionsData collected to date reveal Plcg2*M28L on a LOAD1 background showed fewer sex‐dependent change in metabolism, perfusion and uncoupling on HFD when compared to LOAD1. These data suggest that the Plcg2*M28L risk variant on the LOAD1 background may result in an attenuated TREM2 signaling.

Dynamic Changes in Brain Perfusion after Cognitive Rehabilitation in Patients with Type 1 and Type 2 Diabetes Mellitus

INTRODUCTION: The results of numerous studies indicate a high prevalence of cognitive impairment among patients with diabetes mellitus (DM).
 AIM: To evaluate the effectiveness of computerized training in cognitive rehabilitation in individuals with type 1 and type 2 DM, taking into account the dynamics of brain perfusion.
 MATERIALS AND METHODS: A randomized controlled study. The study group consisted of 25 patients with type 1 DM and 30 patients with type 2 DM aged 23 to 67 years. The comparison group included 20 patients with type 1 DM (mean age 28.4 years) and 20 patients with type 2 DM (mean age 56.0 years). Before and after the rehabilitation course, the patients of the study group underwent a general clinical examination, a blood test for carbohydrate metabolism, cognitive function testing using the Montreal Scale (MoCA test), contrast-free perfusion magnetic resonance imaging (MRI) of the brain. Active rehabilitation lasted 6 month; it was based on a computerized training, including exercises on verbal and nonverbal intelligence.
 RESULTS: On the initial examination, all the subjects did not have the achieved target level of glycated hemoglobin. After completion of the training program, a decrease in the parameter in both groups was noted, as well as a decrease in the mean level of fasting glycemia in people with type 1 DM. The result of neuropsychological testing in all patients at the initial stage corresponded to the diagnosis of ‘cognitive dysfunction’. The control test revealed an improvement in cognitive status according to the overall score, the abstraction scale, speech, memory and visual-constructive skills. Correlation analysis in the group with type 1 DM showed that the result of exercises on visual attention and auditory perception was influenced by memory function. In individuals with type 2 DM, increased glycated hemoglobin was associated with a decrease in cognitive functions according to the overall score of the MoCA test, as well as in tasks for speech, memory, visual-constructive skills. Dynamic analysis of changes in the MRI picture revealed hypoperfusion in the area of the right and left thalamus in patients with type 1 and type 2 DM, respectively, as well as increased perfusion of the white matter of the right parietal lobe in the group with type 1 DM, and in the putamen area on the left in the group with type 2 DM.
 CONCLUSION: In patients with type 1 and type 2 DM, as well as with cognitive deficit, who underwent a course of cognitive rehabilitation using computerized training, an improvement in cognitive status was noted, which was confirmed by the results of contrast-free perfusion MRI. to evaluate the effectiveness of computerized training in cognitive rehabilitation in people with type 1 and type 2 diabetes mellitus, taking into account the dynamics of brain perfusion.

Perfusion Imaging and Inflammation Biomarkers Provide Complementary Information in Alzheimer's Disease.

Single photon emission tomography (SPECT) can detect early changes in brain perfusion to support the diagnosis of dementia. Inflammation is a driver for dementia progression and measures of inflammation may further support dementia diagnosis. In this study, we assessed whether combining imaging with markers of inflammation improves prediction of the likelihood of Alzheimer's disease (AD). We analyzed 91 participants datasets (Institutional Ethics Approval 20/NW/0222). AD biomarkers and markers of inflammation were measured in cerebrospinal fluid. Statistical parametric mapping was used to quantify brain perfusion differences in perfusion SPECT images. Logistic regression models were trained to evaluate the ability of imaging and inflammation markers, both individually and combined, to predict AD. Regional perfusion reduction in the precuneus and medial temporal regions predicted Aβ42 status. Increase in inflammation markers predicted tau and neurodegeneration. Matrix metalloproteneinase-10, a marker of blood-brain barrier regulation, was associated with perfusion reduction in the right temporal lobe. Adenosine deaminase, an enzyme involved in sleep homeostasis and inflammation, was the strongest predictor of neurodegeneration with an odds ratio of 10.3. The area under the receiver operator characteristic curve for the logistic regression model was 0.76 for imaging and 0.76 for inflammation. Combining inflammation and imaging markers yielded an area under the curve of 0.85. Study results showed that markers of brain perfusion imaging and markers of inflammation provide complementary information in AD evaluation. Inflammation markers better predict tau status while perfusion imaging measures represent amyloid status. Combining imaging and inflammation improves AD prediction.

Changes in brain perfusion with training-related visuomotor improvement in MS.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. A better understanding of the mechanisms supporting brain plasticity in MS would help to develop targeted interventions to promote recovery. A total of 29 MS patients and 19 healthy volunteers underwent clinical assessment and multi-modal MRI acquisition [fMRI during serial reaction time task (SRT), DWI, T1w structural scans and ASL of resting perfusion] at baseline and after 4-weeks of SRT training. Reduction of functional hyperactivation was observed in MS patients following the training, shown by the stronger reduction of the BOLD response during task execution compared to healthy volunteers. The functional reorganization was accompanied by a positive correlation between improvements in task accuracy and the change in resting perfusion after 4 weeks' training in right angular and supramarginal gyri in MS patients. No longitudinal changes in WM and GM measures and no correlation between task performance improvements and brain structure were observed in MS patients. Our results highlight a potential role for CBF as an early marker of plasticity, in terms of functional (cortical reorganization) and behavioral (performance improvement) changes in MS patients that may help to guide future interventions that exploit preserved plasticity mechanisms.

Is brain perfusion correlated to switching mood states and cognitive impairment in bipolar disorder type I? A longitudinal study using perfusion imaging approach.

Type I Bipolar disorder (BD-I) is a neuropsychiatric disorder characterized by manic or mixed-featured episodes, impaired cognitive functioning, and persistent work and social functioning impairment. This study aimed to investigate within-subject; (i) differences in brain perfusion using Single-photon emission computed tomography (SPECT) between manic and euthymic states in BD-I patients; (ii) explore potential associations between altered brain perfusion and cognitive status; and (iii) examine the relationship between cerebral perfusion and mania symptom ratings. Seventeen adult patients diagnosed with BD-I in a manic episode were recruited, and clinical assessments, cognitive tests, and brain perfusion studies were conducted at baseline (mania state) and a follow-up visit 6 months later. The results showed cognitive impairment during the manic episode, which persisted during the euthymic state at follow-up. However, no significant changes in brain perfusion were observed between the manic and euthymic states. During mania, trends toward decreased perfusion in the left cerebellum and right superior parietal lobule were noted. Additionally, trends indicated a higher perfusion imbalance in the left superior and middle frontal gyrus during mania and the right superior and middle frontal gyrus during euthymia. No significant correlations existed between brain perfusion, mania symptom ratings, and cognitive performance, indicating that symptomatology might represent more than neural hemodynamics. These findings suggest that cognitive impairment may persist in BD-I patients and highlight the need for therapeutic interventions targeting cognitive deficits. More extensive studies with extended follow-up periods are warranted further to investigate brain perfusion and cognitive functioning in BD-I patients.

Differential Implications of Cerebral Hypoperfusion and Hyperperfusion in Parkinson's Disease.

Patients with Parkinson's disease (PD) exhibit widespread brain perfusion changes. This study investigated whether cerebral regions with hypoperfusion and hyperperfusion have differential effects on motor and cognitive symptoms in PD using early-phase 18 F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (18 F-FP-CIT) positron emission tomography (PET) scans. We enrolled 394 patients with newly diagnosed PD who underwent dual-phase 18 F-FP-CIT PET scans. Indices reflecting associated changes in regional cerebral hypoperfusion and hyperperfusion on early-phase 18 F-FP-CIT PET scans were calculated as PD[hypo] and PD[hyper] , respectively. The associations of PD[hypo] and PD[hyper] on motor and cognitive symptoms at baseline were assessed using multivariate linear regression. Also, Cox regression and linear mixed models were performed to investigate the effects of baseline PD[hypo] and PD[hyper] on longitudinal outcomes. There was a weak correlation between PD[hypo] and PD[hyper] (γ = -0.19, P < 0.001). PD[hypo] was associated with baseline Unified Parkinson's Disease Rating Scale Part III scores (β = -1.02, P = 0.045), rapid increases in dopaminergic medications (β = -18.02, P < 0.001), and a higher risk for developing freezing of gait (hazard ratio [HR] = 0.67, P = 0.019), whereas PD[hyper] was not associated. Regarding cognitive function, PD[hypo] was more relevant to the baseline cognitive performance levels of visuospatial, memory, and frontal/executive function than PD[hyper] . However, greater PD[hyper] was associated with future dementia conversion (HR = 1.43, P = 0.004), whereas PD[hypo] was not associated. These findings suggest that PD[hypo] and PD[hyper] may differentially affect motor and cognitive functions in patients with PD. © 2023 International Parkinson and Movement Disorder Society.

White and Gray Matter Perfusion in Children with Moyamoya Angiopathy after Revascularization Surgery

Introduction: Surgical revascularization is very effective in patients with moyamoya angiopathy (MMA) and leads to improvements in cortical perfusion parameters. However, changes in white matter hemodynamics are still underestimated. To date, only a few studies have examined brain perfusion changes within deep white matter after bypass surgery in patients with MMA. Methods: Ten children with MMA were evaluated using the CT perfusion technique before and after revascularization surgery. Brain perfusion parameters within gray and white matter were compared before and after surgery. The correlations between the perfusion parameters before surgery and the Suzuki stage, as well as between the perfusion parameters and the cognitive scores, were also evaluated. Results: Brain perfusion parameters improved significantly in both gray matter (predominantly due to cerebral blood flow within the anterior circulation, p < 0.01) and white matter (predominantly due to cerebral blood volume within the semiovale centrum, p < 0.001). We revealed that the pattern of improvement in perfusion in white matter differed from the pattern of improvement in perfusion in gray matter. Significant correlations were revealed between the Suzuki stage before surgery and the perfusion parameters within the posterior cerebral artery circulation (adjusted p < 0.05). There were also significant correlations between cognitive scores and brain perfusion parameters in gray matter and white matter (adjusted p < 0.05). Conclusions: The perfusion parameters of gray matter and white matter in the brain improve differently after bypass surgery in patients with MMA. Different hemodynamics within these compartments could explain this.

Longitudinal Alterations of Cerebral Blood Flow in High-Contact Sports.

Repetitive head trauma is common in high-contact sports. Cerebral blood flow (CBF) can measure changes in brain perfusion that could indicate injury. Longitudinal studies with a control group are necessary to account for interindividual and developmental effects. We investigated whether exposure to head impacts causes longitudinal CBF changes. We prospectively studied 63 American football (high-contact cohort) and 34 volleyball (low-contact controls) male collegiate athletes, tracking CBF using 3D pseudocontinuous arterial spin labeling magnetic resonance imaging for up to 4 years. Regional relative CBF (rCBF, normalized to cerebellar CBF) was computed after co-registering to T1-weighted images. A linear mixed effects model assessed the relationship of rCBF to sport, time, and their interaction. Within football players, we modeled rCBF against position-based head impact risk and baseline Standardized Concussion Assessment Tool score. Additionally, we evaluated early (1-5 days) and delayed (3-6 months) post-concussion rCBF changes (in-study concussion). Supratentorial gray matter rCBF declined in football compared with volleyball (sport-time interaction p = 0.012), with a strong effect in the parietal lobe (p = 0.002). Football players with higher position-based impact-risk had lower occipital rCBF over time (interaction p = 0.005), whereas players with lower baseline Standardized Concussion Assessment Tool score (worse performance) had relatively decreased rCBF in the cingulate-insula over time (interaction effect p = 0.007). Both cohorts showed a left-right rCBF asymmetry that decreased over time. Football players with an in-study concussion showed an early increase in occipital lobe rCBF (p = 0.0166). These results suggest head impacts may result in an early increase in rCBF, but cumulatively a long-term decrease in rCBF. ANN NEUROL 2023.

Hyperbaric Oxygen Therapy versus placebo for post-concussion syndrome (HOT-POCS): A randomized, double-blinded controlled pilot study

Post-Concussion Syndrome (PCS) refers to the persistence of physical, cognitive, and emotional symptoms following mild traumatic brain injury (mTBI)/concussion, occurring in roughly 15–30% of individuals. Hyperbaric oxygen therapy (HBOT) has been suggested as a potential treatment for PCS; however, the evidence to date is mixed due to inconsistencies in the treatment protocol and focus on veterans with combat-related injuries, which may not be generalizable to the general population. The goal of Hyperbaric Oxygen Therapy for Post-Concussion Syndrome (HOT-POCS) is to assess the efficacy and safety of HBOT for the treatment of PCS in the civilian population. This randomized, controlled pilot study will be using a standardized HBOT protocol (20 sessions of 100% O2 at 2.0 atm absolute [ATA]) compared with a true placebo gas system that mimics the oxygen composition at room air (20 sessions of 10.5% O2 and 89.5% nitrogen at 2.0 ATA) in a cohort of 100 adults with persistent post-concussive symptoms 3–12 months following injury. Change in symptoms on the Rivermead Post-concussion Questionnaire (RPQ) will be the primary outcome of interest. Secondary outcomes include the rate of adverse events, change in the quality of life, and change in cognitive function. Exploratory outcome measures will include changes in physical function and changes in cerebral brain perfusion and oxygen metabolism on MRI brain imaging. Overall, the HOT-POCS study will compare the efficacy of a standardized HBOT treatment protocol against a true placebo gas for the treatment of PCS within 12 months after injury.

Cerebral blood flow changes in schizophrenia patients with auditory verbal hallucinations during low-frequency rTMS treatment.

Auditory verbal hallucinations (AVH) are a prominent symptom of schizophrenia. Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been evidenced to improve the treatment of AVH in schizophrenia. Although abnormalities in resting-state cerebral blood flow (CBF) have been reported in schizophrenia, the perfusion alterations specific to schizophrenia patients with AVH during rTMS require further investigation. In this study, we used arterial spin labeling (ASL) to investigate changes in brain perfusion in schizophrenia patients with AVH, and their associations with clinical improvement following low-frequency rTMS treatment applied to the left temporoparietal junction area. We observed improvements in clinical symptoms (e.g., positive symptoms and AVH) and certain neurocognitive functions (e.g., verbal learning and visual learning) following treatment. Furthermore, at baseline, the patients showed reductions in CBF in regions associated with language, sensory, and cognition compared to controls, primarily located in the prefrontal cortices (e.g., left inferior frontal gyrus and left middle frontal gyrus), occipital lobe (e.g., left calcarine cortex), and cingulate cortex (e.g., bilateral middle cingulate cortex), compared to controls. Conversely, we observed increased CBF in the left inferior temporal gyrus and bilateral putamen in patients relative to controls, regions known to be involved in AVH. However, the hypoperfusion or hyperperfusion patterns did not persist and instead were normalized, and were related to clinical response (e.g., AVH) in patients during low-frequency rTMS treatment. Importantly, the changes in brainperfusion were related to clinical response (e.g., AVH) in patients. Our findings suggest that low-frequency rTMS can regulate brain perfusion involving critical circuits by its remote effect in schizophrenia, and may play an important mechanistic role in the treatment of AVH.

Brain Perfusion Changes in a Patient with Facial Trauma.

A 69-year-old male was admitted to our hospital because of left facial trauma with bone fractures, including the maxillary sinus, zygomatic arch, and ethmoid and sphenoid bones. Brain computed tomography was unremarkable but regional cerebral blood flow with hexamethyl-propylene-amine oxime single-photon emission computed tomography (SPECT) showed hypoperfusion of the left hemisphere, which was reversible since a repeat SPECT 4 months later was substantially improved. Brain perfusion SPECT may provide information on cerebrovascular status in some cases of facial injury.

WED-444 - Liver-associated dysmetabolism is related to brain structure and perfusion changes in obesity: the BARICO study

WED-444 - Liver-associated dysmetabolism is related to brain structure and perfusion changes in obesity: the BARICO study

Levetiracetam Increases Hippocampal Blood Flow in Alzheimer's Disease as Measured by Arterial Spin Labelling MRI.

Patients with Alzheimer's disease (AD) have an increased risk of developing epileptiform discharges, which is associated with a more rapid rate of progression. This suggests that suppression of epileptiform activity could have clinical benefit in patients with AD. In the current study, we tested whether acute, intravenous administration of levetiracetam led to changes in brain perfusion as measured with arterial spin labeling MRI (ASL-MRI) in AD. We conducted a double-blind, within-subject crossover design study in which participants with mild AD (n = 9) received placebo, 2.5 mg/kg, and 7.5 mg/kg of LEV intravenously in a random order in three sessions. Afterwards, the participants underwent ASL-MRI. Analysis of relative cerebral blood flow (rCBF) between 2.5 mg of levetiracetam and placebo showed significant decreases in a cluster that included the posterior cingulate cortex, the precuneus, the posterior part of the cingulate gyrus, while increased cerebral blood flow was found in both temporal lobes involving the hippocampus. Administration of 2.5 mg/kg of LEV in patients without any history of epilepsy leads to changes in rCBF in areas known to be affected in the early stages of AD. These areas may be the focus of the epileptiform activity. Larger studies are needed to confirm the current findings.

Altered coupling of resting-state cerebral blood flow and functional connectivity in Meige syndrome.

Meige syndrome (MS) is an adult-onset segmental dystonia disease, mainly manifested as blepharospasm and involuntary movement caused by dystonic dysfunction of the oromandibular muscles. The changes of brain activity, perfusion and neurovascular coupling in patients with Meige syndrome are hitherto unknown. Twenty-five MS patients and thirty age- and sex-matched healthy controls (HC) were prospectively recruited in this study. All the participants underwent resting-state arterial spin labeling and blood oxygen level-dependent examinations on a 3.0 T MR scanner. The measurement of neurovascular coupling was calculated using cerebral blood flow (CBF)-functional connectivity strength (FCS) correlations across the voxels of whole gray matter. Also, voxel-wised analyses of CBF, FCS, and CBF/FCS ratio images between MS and HC were conducted. Additionally, CBF and FCS values were compared between these two groups in selected motion-related brain regions. MS patients showed increased whole gray matter CBF-FCS coupling relative to HC (t = 2.262, p = 0.028). In addition, MS patients showed significantly increased CBF value in middle frontal gyrus and bilateral precentral gyrus. The abnormal elevated neurovascular coupling of MS may indicate a compensated blood perfusion in motor-related brain regions and reorganized the balance between neuronal activity and brain blood supply. Our results provide a new insight into the neural mechanism underlying MS from the perspective of neurovascular coupling and cerebral perfusion.

Preoperative symptoms of depression, anxiety, and cognitive impairment in glioma patients: A cerebral perfusion CT study.

Glioma patients have varying degrees of psychiatric symptoms, which severely affect the quality of life of patients and their families. The present study investigated the correlation between preoperative psychiatric symptoms and local cerebral perfusion parameters of in glioma patients. The depression, anxiety, and cognitive impairment (CI) scores of 39 patients were assessed separately, and all of the patients underwent a preoperative perfusion computed tomography scan. This study found that: (1) The incidence of preoperative symptoms of depression, anxiety, and CI was 46.15%, 48.72%, and 25.64%, respectively. (2) Cerebral blood volume (CBV) (lesion-sided [LS] occipital lobe white matter [WM] and parietal lobe WM and normal-sided temporal lobe WM), permeability surface (PS) (LS temporal lobe gray matter [GM] and parietal lobe WM) in the depression group were significantly decreased (p<.05). (3) CBV (LS occipital lobe WM), cerebral blood flow (LS parietal lobe GM, centrum ovale and frontal lobe WM and normal-sided frontal lobe WM, temporal lobe WM and parietal lobe WM), and mean transition time (MTT) (normal-sided frontal lobe WM and temporal lobe WM) in the anxiety group were significantly increased (p<.05). (4) CBV (LS temporal lobe GM), MTT (LS anterior limb of internal capsule), and PS (LS thalamus) in the CI group were significantly increased (p<.05). This study showed that glioma patients had different levels of psychological distress in glioma patients before surgery, which may be related to the changes in brain perfusion caused by the tumor.

PRELIMINARY ANALYSIS OF BRAIN PERFUSION OBTAINED WITH ARTERIAL SPIN LABELING METHOD (ASL) USED TO EVALUATE THE EFFECTS OF TYPE 2 DIABETES IN MORBIDLY OBESE PATIENTS

Introduction: Earlier studies demonstrated that obesity was associated with lower cerebral perfusion in obese participants, as compared to participants at normal weight, especially in frontal grey matter regions. On the other hand, type 2 diabetes is a common co-morbid condition among obese patients, and it is associated per se with brain structural and metabolic abnormalities that are related to lower cerebral blood flow (CBF). Unfortunately, only two studies evaluated the effects on co-morbid T2D on CBF, one of them in adolescent population. Therefore, the aim of this study was to establish a pipeline process to quantify CBF images that were obtained in an independent project evaluating brain abnormalities associated with morbid obesity and their resolution with intragastric balloon – an invasive method to reduce weight. Furthermore, we compared CBF between obese patients with and without type 2 diabetes, as well as controls at normal weight. Methods: A processing pipeline utilizing SPM12 toolbox and digital maps (AAL, Brodmann) was established to automatically pre-process scans and toolbox REX was used to prepare data for statistical analysis. We used it to analyze data for six morbidly obese patients with type 2 diabetes T2D (O-T2D) (average age = 48.5 ± 7.9, average body weight = 125.0 ± 29.8 kg, average BMI = 42.0 ± 9.4), eight morbidly obese patients without T2D (O-NT2D) (average age = 39.1 ± 16.1, average body weight = 138.2 ± 14.9 kg, average BMI = 50.2 ± 6.5) and eight healthy controls with normal weight (CON) (average age = 43.5 ± 11.5, average body weight = 67.4 ± 14.6 kg, average BMI = 23.4 ± 3.5). All studies were performed at the CNS Lab MRI Centre, NIBBE. Results: These preliminary analyses demonstrated lower cerebral blood flow in frontal cortex in obese patients with T2D, as compared to obese patients without T2D and controls. Conclusion: A pipeline to numerically process ASL-CBF data was created and used to analyse the small dataset. The analyses indicated that not morbid obesity per se, but morbid obesity combined with co-morbid type 2 diabetes is associated with widespread reductions in cerebral perfusion. The results are in line with other studies that were limited to subjects with lower stages of overweight and obesity. We believe that this methodology may be applied to study changes in brain perfusion evoked by simulated hypergravity with Lower Body Negative Pressure (LBNP) device placed within a magnetic resonance scanner or perfusion changes induced by hypoxia.