Post-operative changes of cerebral circulation and metabolism in the acute stage of low-grade aneurysmal subarachnoid hemorrhage

Abstract

Objective: Pre- and post-operative cerebral circulation and metabolism were evaluated in patients with low-grade acute aneurysmal subarachnoid hemorrhage (SAH) who underwent early surgery to investigate the effects on brain dysfunction.

Methods: Positron emission tomography (PET) was performed to measure the regional cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO₂), oxygen extraction fraction (OEF) and cerebral blood volume in four patients (one male and three females, mean age: 60.3 years) with low-grade SAH within 30 hours of onset. Post-operative PET was performed on the seventh post-operative day. No patient suffered clinical deterioration during the study. Pre-operative PET scans demonstrated significant global reduction of CBF and CMRO₂, compared to 16 normal control subjects, and no significant change in OEF. CBF and CMRO₂ reduction post-operatively improved to the normal control values. Post-operative OEF was significantly increased compared to the normal control value.

Conclusions: Patients with low-grade SAH have impairment of cerebral circulation and metabolism in the acute period, which improves after surgery. Early surgery for low-grade SAH, necessary to avoid rerupture of the aneurysm, did not worsen the impairment of cerebral circulation and metabolism. However, measures to protect the brain from perioperative damage are necessary to achieve the optimum outcome.     

Noninvasive imaging of brain oxygen metabolism in children with primary nocturnal enuresis during natural sleep

A series of studies have revealed that nocturnal enuresis is closely related to hypoxia in children with primary nocturnal enuresis (PNE). However, brain oxygen metabolism of PNE children has not been investigated before. The purpose of this study was to investigate changes in whole‐brain cerebral metabolic rate of oxygen (CMRO₂), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) in children suffering from PNE. We used the newly developed T2‐relaxation‐under‐spin‐tagging (TRUST) magnetic resonance imaging technique. Neurological evaluation, structural imaging, phase‐contrast, and the TRUST imaging method were applied in children with PNE (n = 37) and healthy age‐ and sex‐matched control volunteers (n = 39) during natural sleep to assess whole‐brain CMRO₂, CBF, OEF, and arousal from sleep scores. Results showed that whole‐brain CMRO₂ and OEF values of PNE children were higher in controls, while there was no significant difference in CBF. Consequently, OEF levels of PNE children were increased to maintain oxygen supply. The elevation of OEF was positively correlated with the difficulty of arousal. Our results provide the first evidence that high oxygen consumption and high OEF values could make PNE children more susceptible to hypoxia, which may induce cumulative arousal deficits and make them more prone to nocturnal enuresis. Hum Brain Mapp 38:2532–2539, 2017. © 2017 Wiley Periodicals, Inc.     

Cerebral blood flow and metabolism in patients with silent brain infarction: occult misery perfusion in the cerebral cortex

OBJECTIVES—Silentbrain infarction (SBI) is of growing interest as a possible risk factorfor symptomatic stroke. Although morphological characteristics of SBIhave been well defined, their characteristic patterns of cerebral bloodflow (CBF) and metabolism are in dispute. The purpose of this study wasto elucidate CBF and metabolism in patients with SBI in relation tosymptomatic stroke.
METHODS—The patientsunderwent PET and were separated into three groups; control group (Cgroup), with no lesions on CT (n=9, mean age 57), SBI group, with noneurological signs or history of stroke, but with ischaemic lesions onCT (n=9, mean age 63), and brain infarction group (BI group), withneurological deficits and compatible CT lesions in the area supplied byperforating arteries (n=19, mean age 56). Regional CBF, oxygenextraction fraction (OEF), cerebral metabolic rate for oxygen(CMRO₂), and cerebral blood volume (CBV) were measured by PET.
RESULTS—Mean valuesfor CBF to the cerebral cortex and deep grey matter were lower in theSBI group (31.6 (SD 5.8) and 34.3 (SD 6.9) ml/100 g/min, respectively)and in the BI group (30.8 (SD 5.2), 33.9 (SD 5.9), respectively) thanin the C group (36.0 (SD 6.6) and 43.5 (SD 9.5), respectively).Although mean CMRO₂ of deep grey matter (2.36 (SD 0.52)ml/100 g/min) was significantly decreased in the SBI group comparedwith the C group (2.76 (SD 0.480), p<0.01), CMRO₂ of thecortical area was as well preserved in the SBI patients (2.36 (SD0.39)) as in the controls (2.48 (SD 0.32)) with a compensatory increaseof mean OEF (0.45 (SD 0.06) and 0.41 (SD 0.05), respectively).
CONCLUSIONS—Patientswith SBI showed decreased CBF and CMRO₂ in deep greymatter. On the other hand, decreased CBF with milder increased OEF,resulting in preserved CMRO₂ in the cerebral cortexindicates the presence of occult misery perfusion, suggesting thatpatients with SBI have reduced cerebral perfusional reserves.

     

Metabolic control of resting hemispheric cerebral blood flow is oxidative,not glycolytic

Although the close regional coupling of resting cerebral blood flow (CBF) with both cerebral metabolic rate of oxygen (CMRO₂) and cerebral metabolic rate of glucose (CMRglc) within individuals is well documented, there are few data regarding the coupling between whole brain flow and metabolism among different subjects. To investigate the metabolic control of resting whole brain CBF, we performed multivariate analysis of hemispheric CMRO₂, CMRglc, and other covariates as predictors of resting CBF among 23 normal humans. The univariate analysis showed that only CMRO₂ was a significant predictor of CBF. The final multivariate model contained two additional terms in addition to CMRO₂: arterial oxygen content and oxygen extraction fraction. Notably, arterial plasma glucose concentration and CMRglc were not included in the final model. Our data demonstrate that the metabolic factor controlling hemispheric CBF in the normal resting brain is CMRO₂ and that CMRglc does not make a contribution. Our findings provide evidence for compartmentalization of brain metabolism into a basal component in which CBF is coupled to oxygen metabolism and an activation component in which CBF is controlled by another mechanism.     

Paradoxical reduction of cerebral blood flow after acetazolamide loading: a hemodynamic and metabolic study with 15O PET

Paradoxical reduction of cerebral blood flow (CBF) after administration of the vasodilator acetazolamide is the most severe stage of cerebrovascular reactivity failure and is often associated with an increased oxygen extraction fraction (OEF). In this study, we aimed to reveal the mechanism underlying this phenomenon by focusing on the ratio of CBF to cerebral blood volume (CBV) as a marker of regional cerebral perfusion pressure (CPP). In 37 patients with unilateral internal carotid or middle cerebral arterial (MCA) steno-occlusive disease and 8 normal controls, the baseline CBF (CBF_b), CBV, OEF, cerebral oxygen metabolic rate (CMRO₂), and CBF after acetazolamide loading in the anterior and posterior MCA territories were measured by ¹⁵O positron emission tomography. Paradoxical CBF reduction was found in 28 of 74 regions (18 of 37 patients) in the ipsilateral hemisphere. High CBF_b (>47.6 mL/100 mL/min, n = 7) was associated with normal CBF_b/CBV, increased CBV, decreased OEF, and normal CMRO₂. Low CBF_b (<31.8 mL/100 mL/min, n = 9) was associated with decreased CBF_b/CBV, increased CBV, increased OEF, and decreased CMRO₂. These findings demonstrated that paradoxical CBF reduction is not always associated with reduction of CPP, but partly includes high-CBF_b regions with normal CPP, which has not been described in previous studies.     

Early Derangements in Oxygen and Glucose Metabolism Following Head Injury: The Ischemic Penumbra and Pathophysiological Heterogeneity

Introduction  Conclusive evidence of cerebral ischemia following head injury has been elusive. We aimed to use ¹⁵O and ¹⁸Fluorodeoxyglucose positron emission tomography (PET) to investigate pathophysiological derangements following head injury. Results   Eight patients underwent PET within 24 h of injury to map cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO₂), oxygen extraction fraction (OEF), and cerebral glucose metabolism (CMRglc). Physiological regions of interest (ROI) were generated for each subject using a range of OEF values from very low (<10), low (10–30), normal range (30–50), high (50–70), and critically high (≥70%). We applied these ROIs to each subject to generate data that would examine the balance between blood flow and metabolism across the injured brain independent of structural injury. Discussion   Compared to the normal range, brain regions with higher OEF demonstrate a progressive CBF reduction (P < 0.01), CMRO₂ increase (P < 0.05), and no change in CMRglc, while regions with lower OEF are associated with reductions in CBF, CMRO₂, and CMRglc (P < 0.01). Although all subjects demonstrate a decrease in CBF with increases in OEF > 70%, CMRO₂ and CMRglc were generally unchanged. One subject demonstrated a reduction in CBF and small fall in CMRO₂ within the high OEF region (>70%), combined with a progressive increase in CMRglc. Conclusions  The low CBF and maintained CMRO₂ in the high OEF ROIs is consistent with classical cerebral ischemia and the presence of an ‘ischemic penumbra’ following early head injury, while the metabolic heterogeneity that we observed suggests significant pathophysiological complexity. Other mechanisms of energy failure are clearly important and further study is required to delineate the processes involved.     

Dual role of cerebral blood flow in regional brain temperature control in the healthy newborn infant

Small shifts in brain temperature after hypoxia–ischaemia affect cell viability. The main determinants of brain temperature are cerebral metabolism, which contributes to local heat production, and brain perfusion, which removes heat. However, few studies have addressed the effect of cerebral metabolism and perfusion on regional brain temperature in human neonates because of the lack of non-invasive cot-side monitors. This study aimed (i) to determine non-invasive monitoring tools of cerebral metabolism and perfusion by combining near-infrared spectroscopy and echocardiography, and (ii) to investigate the dependence of brain temperature on cerebral metabolism and perfusion in unsedated newborn infants.Thirty-two healthy newborn infants were recruited. They were studied with cerebral near-infrared spectroscopy, echocardiography, and a zero-heat flux tissue thermometer. A surrogate of cerebral blood flow (CBF) was measured using superior vena cava flow adjusted for cerebral volume (rSVC flow). The tissue oxygenation index, fractional oxygen extraction (FOE), and the cerebral metabolic rate of oxygen relative to rSVC flow (CMRO₂ index) were also estimated.A greater rSVC flow was positively associated with higher brain temperatures, particularly for superficial structures. The CMRO₂ index and rSVC flow were positively coupled. However, brain temperature was independent of FOE and the CMRO₂ index. A cooler ambient temperature was associated with a greater temperature gradient between the scalp surface and the body core.Cerebral oxygen metabolism and perfusion were monitored in newborn infants without using tracers. In these healthy newborn infants, cerebral perfusion and ambient temperature were significant independent variables of brain temperature. CBF has primarily been associated with heat removal from the brain. However, our results suggest that CBF is likely to deliver heat specifically to the superficial brain. Further studies are required to assess the effect of cerebral metabolism and perfusion on regional brain temperature in low-cardiac output conditions, fever, and with therapeutic hypothermia.     

Interindividual variations of cerebral blood flow, oxygen delivery, and metabolism in relation to hemoglobin concentration measured by positron emission tomography in humans

Regional cerebral blood flow (CBF) and oxygen metabolism can be measured by positron emission tomography (PET) with ¹⁵O-labeled compounds. Hemoglobin (Hb) concentration of blood, a primary determinant of arterial oxygen content (C_aO₂), influences cerebral circulation. We investigated interindividual variations of CBF, cerebral blood volume (CBV), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO₂) in relation to Hb concentration in healthy human volunteers (n=17) and in patients with unilateral steno-occlusive disease (n=44). For the patients, data obtained only from the contralateral hemisphere (normal side) were analyzed. The CBF and OEF were inversely correlated with Hb concentration, but CMRO₂ was independent of Hb concentration. Oxygen delivery defined as a product of C_aO₂ and CBF (C_aO₂ CBF) increased with a rise of Hb concentration. The analysis with a simple oxygen model showed that oxygen diffusion parameter (L) was constant over the range of Hb concentration, indicating that a homeostatic mechanism controlling CBF is necessary to maintain CMRO₂. The current findings provide important knowledge to understand the control mechanism of cerebral circulation and to interpret the ¹⁵O PET data in clinical practice.     

Ischemic brain metabolism in patients with chronic cerebrovascular disease: Increased oxygen extraction fraction and cerebrospinal fluid lactate

The aim of the present study is to elucidate the existence of chronically ischemic metabolism concomitant with misery perfusion of the brain in patients with chronic cerebrovascular disease. For this purpose, we measured cerebral blood flow (CBF) and oxygen metabolism by positron emission tomography (PET) and also determined cerebrospinal fluid (CSF) lactate as an indicator of the ischemic brain metabolism. Twenty-eight patients with chronic ischemic stroke and transient ischemic attack (TIA), who had angiographically occlusive (n = 11), stenotic (n = 10), and nonstenotic changes (n = 7) of the carotid artery and/or the intracranial major artery, were selected for this study. CBF, oxygen extraction fraction (OEF), cerebral metabolic rate for oxygen (CMRO₂), and cerebral blood volume (CBV) were determined by PET, and CSF lactate and pyruvate were determined by enzymatic method in the patients with various grades of stenotic changes of the carotid artery. There were no significant differences in PET parameters and CSF variables among the groups of the occlusive, stenotic, and nonstenotic carotid artery. However, CSF lactate was correlated negatively with mean bilateral hemispheric (m)CBF (R² = 0.229, P<.01), positively with mOEF (R² = 0.278, P<.005) and more highly with mCMRO₂/CBF (absolute extraction of oxygen content to the brain) (R² = 0.473, P<.0001) in all patients. There was no correlation between CSF lactate and mCMRO₂ or mCBV. None of the cases in the nonstenotic group showed mOEF greater than 0.45, or mCMRO₂/CBF greater than 7.9 vol%, while 80% of the cases in the stenotic group and 82% of the cases in the occlusive group showed mOEF and mCMRO₂/CBF exceeding the above-mentioned values, respectively. The present findings, that increased mOEF and mCMRO₂/CBF were significantly correlated with increased CSF lactate, indicate the brain to be in a metabolically ischemic state or increased anaerobic glycolysis with oxygen metabolism maintained in patients with chronic ischemic stroke.     

Acute effect of glucose on cerebral blood flow,blood oxygenation,and oxidative metabolism

While it is known that specific nuclei of the brain, for example hypothalamus, contain glucose‐sensing neurons thus their activity is affected by blood glucose level, the effect of glucose modulation on whole‐brain metabolism is not completely understood. Several recent reports have elucidated the long‐term impact of caloric restriction on the brain, showing that animals under caloric restriction had enhanced rate of tricarboxylic acid cycle (TCA) cycle flux accompanied by extended life span. However, acute effect of postprandial blood glucose increase has not been addressed in detail, partly due to a scarcity and complexity of measurement techniques. In this study, using a recently developed noninvasive MR technique, we measured dynamic changes in global cerebral metabolic rate of O₂ (CMRO₂) following a 50 g glucose ingestion (N = 10). A time dependent decrease in CMRO₂ was observed, which was accompanied by a reduction in oxygen extraction fraction (OEF) with unaltered cerebral blood flow (CBF). At 40 min post‐ingestion, the amount of CMRO₂ reduction was 7.8 ± 1.6%. A control study without glucose ingestion was performed (N = 10), which revealed no changes in CMRO₂, CBF, or OEF, suggesting that the observations in the glucose study was not due to subject drowsiness or fatigue after staying inside the scanner. These findings suggest that ingestion of glucose may alter the rate of cerebral metabolism of oxygen in an acute setting. Hum Brain Mapp 36:707–716, 2015. © 2014 Wiley Periodicals, Inc .     

Reduced cerebellar blood flow and oxygen metabolism in spinocerebellar degeneration: a combined PET and MRI study

Fourteen patients with spinocerebellar degeneration (SCD) were subjected to MRI and PET studies. The quantitative MRI data revealed significant cerebellar and pontine atrophy in the patients with olivopontocerebellar atrophy (OPCA), and cerebellar atrophy in the patients with late cerebellar cortical atrophy (LCCA). We failed to demonstrate significant differences in the pons between LCCA patients and normal controls. PET measurements revealed decreases in cerebral oxygen metabolic rate (CMRO₂) in the cerebellar hemisphere and vermis in both groups of patients. The markedly decreased cerebral blood flow (CBF) and CMRO₂ in the pons were found only in the patients with OPCA. PET data corrected for the tissue shrinkage on the basis of MRI morphometry indicated a net reduction in cerebellar CMRO₂ and CBE The present study has demonstrated that a combination of functional and anatomical data offers further evidence in favour of the current acceptable classification of SCD based on clinicopathological grounds. Our data further suggest that the amount of atrophy in the cerebellum could not fully account for the decreased metabolic rates observed in PET studies.     

Impaired response of cerebral oxygen metabolism to visual stimulation in Huntington’s disease

Huntington’s disease (HD) is a neurodegenerative disease caused by a CAG triplet repeat expansion in the Huntingtin gene. Metabolic and microvascular abnormalities in the brain may contribute to early physiological changes that subserve the functional impairments in HD. This study is intended to investigate potential abnormality in dynamic changes in cerebral blood volume (CBV) and cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO₂) in the brain in response to functional stimulation in premanifest and early manifest HD patients. A recently developed 3-D-TRiple-acquisition-after-Inversion-Preparation magnetic resonance imaging (MRI) approach was used to measure dynamic responses in CBV, CBF, and CMRO₂ during visual stimulation in one single MRI scan. Experiments were conducted in 23 HD patients and 16 healthy controls. Decreased occipital cortex CMRO₂ responses were observed in premanifest and early manifest HD patients compared to controls (P < 0.001), correlating with the CAG-Age Product scores in these patients (R² = 0.4, P = 0.001). The results suggest the potential value of this reduced CMRO₂ response during visual stimulation as a biomarker for HD and may illuminate the role of metabolic alterations in the pathophysiology of HD.     

Preserved acetazolamide reactivity in lacunar patients with severe white-matter lesions: 15O-labeled gas and H2O positron emission tomography studies

Limited evidence exists on the relationships between severity of white-matter lesions (WMLs) and cerebral hemodynamics in patients without major cerebral artery disease. To examine changes of cerebral blood flow (CBF), oxygen metabolism, and vascular reserve capacity associated with severity of WML in patients with lacunar stroke, we used a positron emission tomography (PET). Eighteen lacunar patients were divided into two groups according to the severity of WMLs, assessed by Fazekas classification; grades 0 to 1 as mild WML group and grades 2 to 3 as severe WML group. Rapid dual autoradiography was performed with ¹⁵O-labeled gas-PET followed by ¹⁵O-labeled water-PET with acetazolamide (ACZ) challenge. Compared with the mild WML group, the severe WML group showed lower CBF (20.6±4.4 versus 29.9±8.2 mL/100 g per minute, P=0.008), higher oxygen extraction fraction (OEF) (55.2±7.4 versus 46.7±5.3%, P=0.013), and lower cerebral metabolic rate of oxygen (CMRO₂) (1.95±0.41 versus 2.44±0.42 mL/100 g per minute, P=0.025) in the centrum semiovale. There were no significant differences in the ACZ reactivity between the two groups (48.6±22.6% versus 42.5±17.2%, P=0.524). Lacunar patients with severe WMLs exhibited reduced CBF and CMRO₂, and increased OEF in the centrum semiovale. The ACZ reactivity was preserved in both patients with severe and mild WMLs in each site of the brain.     

A computational model of oxygen transport in the cerebrocapillary levels for normal and pathologic brain function

The oxygen exchange and correlation between the cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMRO₂) in the cortical capillary levels for normal and pathologic brain functions remain the subject of debate. A 3D realistic mesoscale model of the cortical capillary network (non-tree like) is constructed using a random Voronoi tessellation in which each edge represents a capillary segment. The hemodynamics and oxygen transport are numerically simulated in the model, which involves rheological laws in the capillaries, oxygen diffusion, and non-linear binding of oxygen to hemoglobin, respectively. The findings show that the cerebral hypoxia due to a significant decreased perfusion (as can occur in stroke) can be avoided by a moderate reduction in oxygen demand. Oxygen extraction fraction (OEF) can be an important indicator for the brain oxygen metabolism under normal perfusion and misery-perfusion syndrome (leading to ischemia). The results demonstrated that a disproportionately large increase in blood supply is required for a small increase in the oxygen demand, which, in turn, is strongly dependent on the resting OEF. The predicted flow-metabolism coupling in the model supports the experimental studies of spatiotemporal stimulations in humans by positron emission tomography and functional magnetic resonance imaging.     

Smoking normalizes cerebral blood flow and oxygen consumption after 12-hour abstention

Acute nicotine administration stimulates [¹⁴C]deoxyglucose trapping in thalamus and other regions of rat brain, but acute effects of nicotine and smoking on energy metabolism have rarely been investigated in human brain by positron emission tomography (PET). We obtained quantitative PET measurements of cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO₂) in 12 smokers who had refrained from smoking overnight, and in a historical group of nonsmokers, testing the prediction that overnight abstinence results in widespread, coupled reductions of CBF and CMRO₂. At the end of the abstention period, global grey-matter CBF and CMRO₂ were both reduced by 17% relative to nonsmokers. At 15 minutes after renewed smoking, global CBF had increased insignificantly, while global CMRO₂ had increased by 11%. Regional analysis showed that CMRO₂ had increased in the left putamen and thalamus, and in right posterior cortical regions at this time. At 60 and 105 minutes after smoking resumption, CBF had increased by 8% and CMRO₂ had increased by 11-12%. Thus, we find substantial and global impairment of CBF/CMRO₂ in abstaining smokers, and acute restoration by resumption of smoking. The reduced CBF and CMRO₂ during acute abstention may mediate the cognitive changes described in chronic smokers.     

Calibrated MRI to evaluate cerebral hemodynamics in patients with an internal carotid artery occlusion

The purpose of this study was to assess whether calibrated magnetic resonance imaging (MRI) can identify regional variances in cerebral hemodynamics caused by vascular disease. For this, arterial spin labeling (ASL)/blood oxygen level-dependent (BOLD) MRI was performed in 11 patients (65±7 years) and 14 controls (66±4 years). Cerebral blood flow (CBF), ASL cerebrovascular reactivity (CVR), BOLD CVR, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO₂) were evaluated. The CBF was 34±5 and 36±11 mL/100 g per minute in the ipsilateral middle cerebral artery (MCA) territory of the patients and the controls. Arterial spin labeling CVR was 44±20 and 53±10% per 10 mm Hg ▵EtCO₂ in patients and controls. The BOLD CVR was lower in the patients compared with the controls (1.3±0.8 versus 2.2±0.4% per 10 mm Hg ▵EtCO₂, P<0.01). The OEF was 41±8% and 38±6%, and the CMRO₂ was 116±39 and 111±40 μmol/100 g per minute in the patients and the controls. The BOLD CVR was lower in the ipsilateral than in the contralateral MCA territory of the patients (1.2±0.6 versus 1.6±0.5% per 10 mmHg ▵EtCO₂, P<0.01). Analysis was hampered in three patients due to delayed arrival time. Thus, regional hemodynamic impairment was identified with calibrated MRI. Delayed arrival artifacts limited the interpretation of the images in some patients.     

Accounting for the role of hematocrit in between‐subject variations of MRI‐derived baseline cerebral hemodynamic parameters and functional BOLD responses

Baseline hematocrit fraction (Hct) is a determinant for baseline cerebral blood flow (CBF) and between‐subject variation of Hct thus causes variation in task‐based BOLD fMRI signal changes. We first verified in healthy volunteers (n = 12) that Hct values can be derived reliably from venous blood T₁ values by comparison with the conventional lab test. Together with CBF measured using phase‐contrast MRI, this noninvasive estimation of Hct, instead of using a population‐averaged Hct value, enabled more individual determination of oxygen delivery (DO₂), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO₂). The inverse correlation of CBF and Hct explained about 80% of between‐subject variation of CBF in this relatively uniform cohort of subjects, as expected based on the regulation of DO₂ to maintain constant CMRO₂. Furthermore, we compared the relationships of visual task‐evoked BOLD response with Hct and CBF. We showed that Hct and CBF contributed 22%–33% of variance in BOLD signal and removing the positive correlation with Hct and negative correlation with CBF allowed normalization of BOLD signal with 16%–22% lower variability. The results of this study suggest that adjustment for Hct effects is useful for studies of MRI perfusion and BOLD fMRI. Hum Brain Mapp 39:344–353, 2018. © 2017 Wiley Periodicals, Inc.     

MRI measurement of angiogenesis and the therapeutic effect of acute marrow stromal cell administration on traumatic brain injury

Using magnetic resonance imaging (MRI), the present study was undertaken to investigate the therapeutic effect of acute administration of human bone marrow stromal cells (hMSCs) on traumatic brain injury (TBI) and to measure the temporal profile of angiogenesis after the injury with or without cell intervention. Male Wistar rats (300 to 350 g, n=18) subjected to controlled cortical impact TBI were intravenously injected with 1 mL of saline (n=9) or hMSCs in suspension (n=9, 3 × 10⁶ hMSCs) 6 hours after TBI. In-vivo MRI acquisitions of T2-weighted imaging, cerebral blood flow (CBF), three-dimensional (3D) gradient echo imaging, and blood-to-brain transfer constant (Ki) of contrast agent were performed on all animals 2 days after injury and weekly for 6 weeks. Sensorimotor function and spatial learning were evaluated. Volumetric changes in the trauma-induced brain lesion and the lateral ventricles were tracked and quantified using T2 maps, and hemodynamic alteration and blood–brain barrier permeability were monitored by CBF and Ki, respectively. Our data show that transplantation of hMSCs 6 hours after TBI leads to reduced cerebral atrophy, early and enhanced cerebral tissue perfusion and improved functional outcome compared with controls. The hMSC treatment increases angiogenesis in the injured brain, which may promote neurologic recovery after TBI.     

Cerebral blood flow and oxygen metabolism in Rett syndrome

Positron emission tomography (PET) was performed in four patients with Rett syndrome (RS) to elucidate the cerebral blood flow and oxygen metabolism. Cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF) were measured quantitatively with HEADTOME-IV using 15O2, C15O2 steady state inhalational technique. As to the correlation between CBF and CMRO2, these four patients were compared with nine cases with other neurological disorders. Case 1, the youngest girl among the patients, showed milder symptoms than others. In all patients, no abnormal findings except for mild brain atrophy were seen on CT. In case 1, values of CBF might be lower for her age than normal values by the report of Kety. OEF was markedly reduced in all regions of three patients with RS (cases 2, 3, 4). These decreased OEF might be caused by reduced oxygen metabolism. However, case 1 which was the youngest and had milder symptoms, showed almost normal values of OEF. The distribution of CBF and CMRO2 was thought not to be abnormal in all patients. On the other hand, there was no discrepancy between CBF and CMRO2 in nine neurological control subjects. Decreased value of OEF was known to be seen in mitochondrial encephalopathy as well as an early stage of cerebral infarction. In mitochondrial encephalopathy, OEF was thought to decrease by reduced oxygen metabolism due to disturbance of aerobic glycolysis. Although the cause of reduced oxygen metabolism in RS was obscure, these results suggested that in RS there was some disturbance of oxygen metabolism of the brain, and values of OEF might be related to clinical status of RS or age.     

Global brain hypoperfusion and oxygenation in amnestic mild cognitive impairment

BackgroundTo determine if global brain hypoperfusion and oxygen hypometabolism occur in patients with amnestic mild cognitive impairment (aMCI).MethodsThirty-two aMCI and 21 normal subjects participated. Total cerebral blood flow (TCBF), cerebral metabolic rate of oxygen (CMRO₂), and brain tissue volume were measured using color-coded duplex ultrasonography (CDUS), near-infrared spectroscopy (NIRS), and MRI. TCBF was normalized by total brain tissue volume (TBV) for group comparisons (nTCBF). Cerebrovascular resistance (CVR) was calculated as mean arterial pressure divided by TCBF.ResultsReductions in nTCBF by 9%, CMRO₂ by 11%, and an increase in CVR by 13% were observed in aMCI relative to normal subjects. No group differences in TBV were observed. nTCBF was correlated with CMRO₂ in normal controls, but not in aMCI.ConclusionsGlobal brain hypoperfusion, oxygen hypometabolism, and neurovascular decoupling observed in aMCI suggest that changes in cerebral hemodynamics occur early at a prodromal stage of Alzheimer's disease, which can be assessed using low-cost and bedside-available CDUS and NIRS technology.