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.     

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.     

Transient global amnesia: implicit/explicit memory dissociation and PET assessment of brain perfusion and oxygen metabolism in the acute stage

OBJECTIVES—To assess explicit memory and twocomponents of implicit memory—that is, perceptual-verbal skilllearning and lexical-semantic priming effects—as well as restingcerebral blood flow (CBF) and oxygen metabolism (CMRO₂)during the acute phase of transient global amnesia.
METHODS—In a 59 year old woman, whose amnesticepisode fulfilled all current criteria for transient global amnesia, aneuropsychological protocol was administered, including word learning,story recall, categorical fluency, mirror reading, and word stemcompletion tasks. PET was performed using the ¹⁵O steadystate inhalation method, while the patient still exhibited severeanterograde amnesia and was interleaved with the cognitive tests.
RESULTS—There was a clear cut dissociationbetween impaired long term episodic memory and preserved implicitmemory for its two components. Categorical fluency was significantlyaltered, suggesting word retrieval strategy—rather than semanticmemory—impairment. The PET study disclosed a reduced CMRO₂with relatively or fully preserved CBF in the left prefrontotemporalcortex and lentiform nucleus, and the reverse pattern over the leftoccipital cortex.
CONCLUSIONS—The PET alterations with patchyCBF-CMRO₂ uncoupling would be compatible with amigraine-like phenomenon and indicate that the isolated assessment ofperfusion in transient global amnesia may be misleading. The pattern ofmetabolic depression, with sparing of the hippocampal area, is oneamong the distinct patterns of brain dysfunction that underlie the(apparently) uniform clinical presentation of transient global amnesia.The finding of a left prefrontal hypometabolism in the face of impairedepisodic memory and altered verbal fluency would fit present dayconcepts from PET activation studies about the role of this area inepisodic and semantic memory encoding/retrieval. Likewise, the changes affecting the lenticular nucleus but sparing the caudate would beconsistent with the normal performance in perceptual-verbal skilllearning. Finally, unaltered lexical-semantic priming effects, despiteleft temporal cortex hypometabolism, suggest that these processes aresubserved by a more distributed neocortical network.

     

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.     

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.     

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.     

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.     

Decreased β-phenylethylamine in CSF in Parkinson's disease

OBJECTIVE—To determine the concentrations ofβ-phenylethylamine (PEA) in CSF in patients with Parkinson'sdisease, and to evaluate the relation between concentration of PEA inCSF and severity of Parkinson's disease.
METHODS—Using gas chromatography-chemicalionisation mass spectrometry, CSF concentrations of PEA were measuredin 23 patients with Parkinson's disease (mean age, 64.0 (SD 8.2)years), of whom three were at Hoehn and Yahr stage II, 11 were at stageIII, and nine were at stage IV. Comparison was made with eight patientswith neuropathy (mean age, 57.0 (SD 19.2) years) and 12 controlswithout neurological disease (mean age, 57.6 (SD 4.8) years).
RESULTS—Concentrations of PEA in CSF inParkinson's disease were significantly lower (mean 205 (SD 131) pg/ml)than in patients with peripheral neuropathy (433 (SD 254) pg/ml) andcontrols (387 (SD 194) pg/ml). The concentrations of PEA in CSFcorrelated negatively with Hoehn and Yahr stage (P<0.01).
CONCLUSIONS—There are decreased CSF concentrationsof PEA in patients with Parkinson's disease.

     

Changes in cerebral blood flow and vasoreactivity in response to acetazolamide in patients with transient global amnesia

OBJECTIVE—Previous reports aboutchanges in cerebral blood flow (CBF) in transient global amnesiadisclosed decreased flow in some parts of the brain. However, CBFanalyses in most reports were qualitative but not quantitative. Thepurpose of this study was to determine changes in CBF in transientglobal amnesia.
METHODS—The CBF was measured and thevasoreactive response to acetazolamide was evaluated in six patientswith transient global amnesia using technetium-99m hexamethylpropyleneamine oxime single-photon emission computed tomography (SPECT). The CBFwas measured during an attack in two patients and soon after anattack in the other four. About one month later, CBF was re-evaluatedin each patient.
RESULTS—Two patients examined during an attackand one patient examined five hours after an attack had increased bloodflow in the occipital cortex and cerebellum. Three patients examined atsix to 10 hours after an attack had decreased blood flow in thethalamus, cerebellum, or putamen. These abnormalities of blood flowalmost disappeared in all patients one month after onset. Thevasodilatory response to acetazolamide, which was evaluated initiallyusing SPECT, was poor in areas of increased blood flow. By the second evaluation of CBF with acetazolamide, the vasodilatory response hadreturned to normal.
CONCLUSIONS—In a patient with transient globalamnesia, CBF increased in the vertebrobasilar territory during theattack and decreased afterwards. The vasodilatory response toacetazolamide may be impaired in the parts of the brain with increasedblood flow. It is suggested that transient global amnesia is distinctfrom migraine but may share the same underlying mechanism.

     

Vasomotor reactivity is exhausted in transient ischaemic attacks with limb shaking

OBJECTIVES—To investigate cerebral vasomotorreactivity in five patients with limb shaking transient ischaemicattacks by using transcranial Doppler sonography.
METHOD—Attacks with transient limb shaking wereunilateral in four patients and bilateral in one. Internal carotidarteries on the side opposite the abnormal limb movements showed three90-95% stenoses and three occlusions as assessed by cerebralangiography in three and magnetic resonance angiography and ultrasoundin one case each. Reactivity of cerebral resistance vessels was studied by measuring peak mean velocities in the middle cerebral artery (MCA)before and after the application of CO₂ enriched air.Reference values were obtained from 25 normal subjects.
RESULTS—During hypercapnia peak mean velocitiesslightly decreased in five MCAs (steal phenomenon) and remainedunchanged in one MCA opposite the abnormal movements, whereas the otherMCAs showed normal reactivities.
CONCLUSION—The delineation of an exhaustedcerebral vasoreactivity in all hemispheres opposite the involuntarylimb movements suggests that haemodynamic failure is the cause oftransient ischaemic attacks with limb shaking.

     

Early nonischemic oxidative metabolic dysfunction leads to chronic brain atrophy in traumatic brain injury

Chronic brain atrophy after traumatic brain injury (TBI) is a well-known phenomenon, the causes of which are unknown. Early nonischemic reduction in oxidative metabolism is regionally associated with chronic brain atrophy after TBI. A total of 32 patients with moderate-to-severe TBI prospectively underwent positron emission tomography (PET) and volumetric magnetic resonance imaging (MRI) within the first week and at 6 months after injury. Regional lobar assessments comprised oxidative metabolism and glucose metabolism. Acute MRI showed a preponderance of hemorrhagic lesions with few irreversible ischemic lesions. Global and regional chronic brain atrophy occurred in all patients by 6 months, with the temporal and frontal lobes exhibiting the most atrophy compared with the occipital lobe. Global and regional reduction in cerebral metabolic rate of oxygen (CMRO₂), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose were observed. The extent of metabolic dysfunction was correlated with the total hemorrhage burden on initial MRI (r=0.62, P=0.01). The extent of regional brain atrophy correlated best with CMRO₂ and CBF. Lobar values of OEF were not in the ischemic range and did not correlate with chronic brain atrophy. Chronic brain atrophy is regionally specific and associated with regional reductions in oxidative brain metabolism in the absence of irreversible ischemia.     

Early single photon emission computed tomography in Sturge-Weber syndrome

OBJECTIVES—Functional cerebral imaging PET and SPECT have shown hypometabolism and hypoperfusion in the area of vascular malformation in children with epilepsy due to Sturge-Weber syndrome. However, data are scarce in infants and do not exist in patients with Sturge-Weber disease without epilepsy. The pattern of perfusion during the first two years of life was studied including patients before the onset of seizures.
METHODS—Twenty two infants with later confirmed Sturge-Weber disease underwent SPECT examination using TOMOMATIC 564 (Medimatic) and xenon-133 at ages ranging from 8 days to 25 months. Twelve had never had seizures before SPECT and seven underwent a second SPECT a mean seven months later. Cerebral blood flow (CBF) was measured in the whole hemisphere and in the part of the cortex involved in the vascular malformation on both sides as well as a ″pathological to normal″ index for the hemisphere and vascular malformation. These values were compared with normal age paired values.
RESULTS—Compared with controls, CBF and the indices in the hemisphere and vascular malformation were significantly decreased in patients who already had had seizures before SPECT, whereas they were significantly increased in 75% of the patients who had never had any seizures. On second SPECT, the indices were decreased in all patients, including the four who still remained non-epileptic.
CONCLUSIONS—SPECT therefore detects CBF asymmetry in infants with Sturge-Weber disease, which tends to shift with age. The cortex involved in the vascular malformation is hyperperfused during the first year of life before first seizures. The classic hypoperfusion appears after one year of age, even in non-epileptic patients.

     

Cerebral blood flow and metabolism of hyperperfusion after cerebral revascularization in patients with moyamoya disease

In moyamoya disease (MMD), surgical revascularization may be complicated with postoperative hyperperfusion. We analyzed cerebral perfusion and metabolism using positron emission tomography (PET) or single-photon emission computed tomography (SPECT) before and after bypass surgery on 42 sides of 34 adult patients with MMD. In seven cases (16.7%) with symptomatic hyperperfusion, diagnosed by qualitative ¹²³I-iodoamphetamine (IMP) SPECT, a subsequent PET study during postoperative subacute stages revealed significantly increased cerebral blood flow (CBF) from 34.1±8.2 to 74.3±12.8 mL/100 g per minute (P<0.01), a persistent increase in cerebral blood volume (CBV) from 5.77±1.67 to 7.01±1.44 mL/100 g and a significant decrease in oxygen extraction fraction (OEF) from 0.61±0.09 to 0.40±0.08 (P<0.01). Mean absolute CBF values during symptomatic hyperperfusion were more than the normal control +2 standard deviations, the predefined criteria of PET. Interestingly, two patients with markedly increased cerebral metabolic rate of oxygen (CMRO₂) at hyperperfusion were complicated with postoperative seizure. Among preoperative PET parameters, increased OEF was the only significant risk factor for symptomatic hyperperfusion (P<0.05). This study revealed that symptomatic hyperperfusion in MMD is characterized by temporary increases in CBF >100% over preoperative values caused by prolonged recovery of increased CBV.     

Changes in tissue oxyhaemoglobin concentration measured using multichannel near infrared spectroscopy during internal carotid angiography

OBJECTIVE—To develop an in vivo model fortesting spatially resolved spectroscopy and quantified near infraredspectroscopy (NIRS) cerebral blood flow measurements.
METHOD—Multiple detector NIRS has been used tostudy changes in tissue oxyhaemoglobin (O₂Hb) concentrationduring selective internal carotid angiography. A significant reductionin O₂Hb occurred in tissue interrogated by detectorssituated between 0.7 and 4.1cm from the NIRS light source.
RESULTS—The time course of O₂Hbconcentration change was consistent with displacement of oxygenatedblood by the radiocontrast medium from vascular beds of differing flowand NIR light attenuation. Increasing changes in O₂Hbconcentration per unit photon path length—predicted to occur atgreater emitter-detector separations if those changes had occurredpredominantly in cerebral tissue—were found in the first four secondsafter injection of radiocontrast medium. However, later changes(6-10 s) were larger and were not proportional to emitter-detector separation.
CONCLUSION—The findings indicate that simpleassumptions regarding the distribution of the internal carotid arteryblood supply to cerebral and extracerebral tissues, the photon pathlength through those tissues, and their relative contributions toattenuation of NIR light may not be justified.

     

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.     

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.     

Frontal cortical synaptophysin in Lewy body diseases: relation to Alzheimer's disease and dementia

OBJECTIVES—Dementia in Alzheimer's diseasecorrelates closely with loss of neocortical synapses. Similar synapticloss has been shown in patients whose Alzheimer's disease is alsoassociated with neocortical and brain stem Lewy bodies. The aim was todetermine if dementia in Lewy body disease was associated withdiminished concentrations of midfrontal cortex synaptophysin.
METHODS—An immunobinding assay was used to measuresynaptophysin in postmortem samples of midfrontal cortex from 89 patients with Alzheimer's disease (ages 59-100, mean 79), 22 withcombined Lewy body disease and Alzheimer's disease (ages69-103, mean 79), 15demented patients with "pure" Lewy bodydisease (ages 57-80, mean 74), nine with neocortical and brainstem Lewy bodies who had Parkinson's disease but were notdemented (ages 68-85, mean 79), and 20 neurologically normal controls(ages 58-89, mean 75). The diagnosis was confirmed in all cases bydetailed neuropathological examination of the contralateral hemibrain.Seven of the patients in the pure Lewy body disease with dementia grouphad initially presented with parkinsonism and eight with dementia.
RESULTS—Synaptophysin concentrations (arbitraryunits (AU)/µg) in patients with Alzheimer's disease (mean 79 (SD28)) or combined Lewy body disease and Alzheimer'sdisease (mean 83 (SD 33)) were significantly lower than in controls(mean 115 (SD 29)) (p=0.002). Synaptophysin concentrations in dementedpatients with pure Lewy body disease (mean 106 SD 39) andpatients with Lewy body disease who were not demented(mean 101 (SD 18)) did not differ significantly from control values orfrom each other.
CONCLUSION—Loss of midfrontal cortex synapsesprobably contributes to dementia in Lewy body disease whenAlzheimer's disease is also present but not to the dementia ofpure Lewy body disease.

     

Altered task-induced cerebral blood flow and oxygen metabolism underlies motor impairment in multiple sclerosis

The neural mechanisms underlying motor impairment in multiple sclerosis (MS) remain unknown. Motor cortex dysfunction is implicated in blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies, but the role of neural–vascular coupling underlying BOLD changes remains unknown. We sought to independently measure the physiologic factors (i.e., cerebral blood flow (ΔCBF), cerebral metabolic rate of oxygen (ΔCMRO₂), and flow–metabolism coupling (ΔCBF/ΔCMRO₂), utilizing dual-echo calibrated fMRI (cfMRI) during a bilateral finger-tapping task. We utilized cfMRI to measure physiologic responses in 17 healthy volunteers and 32 MS patients (MSP) with and without motor impairment during a thumb-button-press task in thumb-related (task-central) and surrounding primary motor cortex (task-surround) regions of interest (ROIs). We observed significant ΔCBF and ΔCMRO₂ increases in all MSP compared to healthy volunteers in the task-central ROI and increased flow–metabolism coupling (ΔCBF/ΔCMRO₂) in the MSP without motor impairment. In the task-surround ROI, we observed decreases in ΔCBF and ΔCMRO₂ in MSP with motor impairment. Additionally, ΔCBF and ΔCMRO₂ responses in the task-surround ROI were associated with motor function and white matter damage in MSP. These results suggest an important role for task-surround recruitment in the primary motor cortex to maintain motor dexterity and its dependence on intact white matter microstructure and neural–vascular coupling.     

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.     

A clinical role for 99mTc-HMPAO SPECT in the investigation of dementia?

OBJECTIVES—To provide the clinician with a guide to the clinical utility of ^99mTc-HMPAO single photon emission computed tomography (SPECT) and to the interpretation of specific test results in the differential diagnosis of dementia.
METHODS—Three hundred and sixty three patients with dementia were studied prospectively for a median three (range 1-6) years and classified into disease groups on the basis of established clinical criteria. The degree to which different patterns of cerebral blood flow (CBF) abnormality found on ^99mTc-HMPAO SPECT imaging at the time of initial patient presentation modified clinical diagnoses was determined by calculating the likelihood ratios for pairwise disease group comparisons. The optimal clinical usage of ^99mTc-HMPAO SPECT was determined by calculating the percentage of significant test results for each pairwise disease group comparison.
RESULTS—Bilateral posterior CBF abnormality was found to significantly increase the odds of a patient having Alzheimer''s disease as opposed to vascular dementia or frontotemporal dementia. Bilateral anterior CBF abnormality significantly increased the odds of a patient having frontotemporal dementia as opposed to Alzheimer''s disease, vascular dementia, or Lewy body disease. "Patchy" CBF changes significantly increased the odds of a patient having vascular dementia as opposed to Alzheimer''s disease. Unilateral anterior, unilateral anterior plus unilateral posterior, and generalised CBF abnormality failed to contribute to the differentiation of any of these forms of dementia.
CONCLUSIONS—^99mTc-HMPAO SPECT was found to be most useful in distinguishing Alzheimer''s disease from vascular dementia and fronto temporal dementia, and least useful in differentiating between Alzheimer''s disease and Lewy body disease, and between vascular dementia, frontotemporal dementia, and progressive aphasia. It is suggested that CBF SPECT should be used selectively and as an adjunct to clinical evaluation and CT.