Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease.

OBJECTIVE: We compared the ability of arterial spin labeling (ASL), an MRI method that measures cerebral blood flow (CBF), to that of FDG-PET in distinguishing patients with Alzheimer disease (AD) from healthy, age-matched controls. METHODS: Fifteen patients with AD (mean age 72 ± 6 years, Mini-Mental State Examination score [MMSE] 20 ± 6) and 19 age-matched controls (mean age 68 ± 6 years, MMSE 29 ± 1) underwent structural MRI. Participants were injected with 5 mCi of FDG during pseudocontinuous ASL scan, which was followed by PET scanning. Statistical parametric mapping and regions of interest (ROI) analysis were used to compare the ability of the 2 modalities in distinguishing patients from controls. Similarity between the 2 modalities was further assessed with linear correlation maps of CBF and metabolism to neuropsychological test scores. RESULTS: Good agreement between hypoperfusion and hypometabolism patterns was observed, with overlap primarily in bilateral angular gyri and posterior cingulate. ROI results showed similar scales of functional deficit between patients and controls in both modalities. Both ASL and FDG-PET were able to distinguish neural networks associated with different neuropsychological tests with good overlap between modalities. CONCLUSIONS: Our voxel-wise results indicated that ASL-MRI provides largely overlapping information with FDG-PET. ROI analysis demonstrated that both modalities detected similar degrees of functional deficits in affected areas. Given its ease of acquisition and noninvasiveness, ASL-MRI may be an appealing alternative for AD studies.

FDG-PET findings in patients with galactosaemia.

Despite treatment with a galactose-restricted diet, many galactosaemia patients develop lifelong cognitive impairment, speech abnormalities and a gamut of neurological problems including cognitive impairment and tremors. No study has explored changes in cerebral glucose metabolism in patients with galactosaemia. Five patients with galactosaemia had ages ranging from 20 to 40 years (mean age 28 years) and eight similarly aged controls received brain [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scans. PET scans were analysed using a previously validated template methodology of regions of interest (ROIs). Count ratios for each anatomical ROI were compared between the galactosaemic patients and the healthy controls. Statistical parametric mapping (SPM) software was also used to further analyse the data. ROI analysis showed that galactosaemic patients had significant bilateral decreases in cerebral glucose metabolism in the superior temporal gyrus, medial occipital lobe, parietal lobe, cerebellum, calcarine cortex, superior frontal cortex, and superior parietal cortex when compared with controls. Significant increases were seen in the cingulate gyrus and temporal poles, bilaterally. SPM analysis revealed foci of decreased glucose metabolism in the caudate, cerebellum, precentral gyrus and cerebellar tonsils of galactosaemic patients. SPM also showed increased glucose metabolism in the subcallosal gyrus and claustrum. The results show significant abnormalities in cerebral function in patients with galactosaemia, particularly with widespread decreases in cortical metabolism. These abnormalities appear to be in brain regions that may be associated with the neuropsychological deficits in these patients. PET brain scans may be of value in galactosaemia patients to evaluate for dysfunction.

The neural basis of the complex mental task of meditation: neurotransmitter and neurochemical considerations.

Meditation is a complex mental process involving changes in cognition, sensory perception, affect, hormones, and autonomic activity. Meditation has also become widely used in psychological and medical practices for stress management as well as a variety of physical and mental disorders. However, until now, there has been limited understanding of the overall biological mechanism of these practices in terms of the effects in both the brain and body. We have previously described a rudimentary neuropsychological model to explain the brain mechanisms underlying meditative experiences. This paper provides a substantial development by integrating neurotransmitter systems and the results of recent brain imaging advances into the model. The following is a review and synthesis of the current literature regarding the various neurophysiological mechanisms and neurochemical substrates that underlie the complex processes of meditation. It is hoped that this model will provide hypotheses for future biological and clinical studies of meditation.

Regional cerebral distribution of [Tc-99m] hexylmethylpropylene amineoxine in patients with progressive aphasia.

Progressive aphasia is a prominent clinical feature of several neurodegenerative disorders. This study used hexylmethylpropylene amineoxine (HMPAO) single photon emission computed tomography (SPECT) to estimate blood flow in areas of the brain that mediate language in patients with progressive aphasia and matched control subjects. The patient population consisted of four men and 12 women with a mean +/- SD age of 69.1 +/- 7.6. Of these, eight were classified as having a nonfluent form of aphasia, whereas the other eight had a fluent form. The patients were compared to 16 healthy volunteers who were studied with an identical protocol. The SPECT images of the brain were acquired with 740 MBq (20 mCi) of Tc-99m-labeled HMPAO on a triple-headed gamma camera equipped with fan beam collimators. The images were analyzed with a set of standardized templates. Mean counts per pixel in 33 regions of interest were compared to the mean counts in the whole supratentorial brain. A laterality index was determined for homotopic regions using the equation 100 x (R - L)/(1/2 x (R - L)). Patients with progressive aphasia had several regions of significantly decreased HMPAO uptake in the left cortex when compared to the homotopic regions on the right. The most prominent deficit in the nonfluent group, as determined by the laterality index, were found in the left dorsolateral prefrontal region (p < 0.05), whereas the most prominent deficits in the group with fluent aphasia were found in the left temporal and parietal language centers (p < 0.05). The left subcortical nuclei were differentially affected, particularly in patients with nonfluent aphasia. The HMPAO SPECT indicates that multiple regions of the left hemisphere are dysfunctional in patients with progressive aphasia. The pattern of perfusion deficits in patients with fluent aphasia appears to be distinct from the pattern in patients with nonfluent aphasia.

Contralateral cortical diaschisis in a patient with cerebellar astrocytoma after radiation therapy.

Contralateral cerebellar diaschisis, hypometabolism in the cerebellum contralateral to a cortical lesion, is a well described phenomenon in patients with stroke and brain tumor. However, few reports exist of patients with cerebellar lesions with the finding of contralateral cortical hypometabolism. The authors present a case of a patient with a right cerebellar astrocytoma after surgical resection and radiation therapy in which fluorine-18 fluorodeoxyglucose positron emission tomographic imaging, performed to rule out recurrent tumor, revealed global hypometabolism in the left cerebral cortex. The concept of contralateral cortical diaschisis and possible mechanisms and clinical implications are reviewed.

Ipsilateral and contralateral thalamic hypometabolism as a predictor of outcome after temporal lobectomy for seizures.

UNLABELLED: FDG PET is often used to help localize the seizure focus before surgery in patients with medically refractory temporal lobe epilepsy. However, the ability of certain patterns of metabolic landscape to predict postsurgical seizure outcome has not been well characterized. The purpose of this retrospective study was to determine whether FDG PET abnormalities elsewhere in the brain, in combination with those in the temporal lobes, can be used to predict seizure outcome after surgery. METHODS: Eighty patients with refractory temporal lobe seizures were imaged with PET after intravenous administration of 115 microCi/kg FDG. Images were interpreted without knowledge of clinical information by an experienced reviewer to determine seizure focus and regional metabolic changes in the brain. Metabolic activity scores were assigned for cortical and subcortical structures using the following criteria: 4 = normal activity, 3 = mildly decreased activity, 2 = moderately decreased activity, 1 = severely decreased activity, and 0 = no activity. A laterality index for each region was calculated using the equation 100 x [right - left]/[1/2 x (right + left)]. Seizure focus localization was based on the laterality of temporal lobe metabolic activity and was compared with that determined by scalp and depth electrodes and MRI results. Comparisons were made between asymmetries in metabolic activity in various brain structures and postoperative seizure frequency. Postoperative outcome was determined on the basis of cessation (complete disappearance of seizures) or continuation of seizure activity, regardless of frequency, compared with the preoperative state. RESULTS: All 64 patients who were free of seizures postoperatively had either no thalamic asymmetry or reduced metabolism on the side from which the temporal lobe was removed. In contrast, 5 of 16 patients (31%) with postoperative seizures of any frequency had hypometabolism in the thalamus contralateral to that of the removed temporal lobe. All 5 patients with reverse thalamic asymmetry had postoperative seizures. Patients with thalamic hypometabolism ipsilateral to the removed temporal lobe also had an increased risk of postoperative seizures, but this risk was not as high as in patients with the contralateral abnormality. In these patients, the temporal lobe (which appeared hypometabolic on PET) was determined to be the site of the seizure on the basis of information besides that provided by PET before surgery. CONCLUSION: This study indicated that, in patients with temporal lobe epilepsy, thalamic metabolic asymmetry, particularly in the reverse direction to that of the temporal lobe asymmetry, was associated with a poor postsurgical outcome compared with no or matched asymmetry. This determination may be important in evaluating patients for, and selecting optimal candidates for, surgical intervention.

Changes in the central nervous system during long-duration space flight: implications for neuro-imaging.

The purpose of this paper is to review the potential functional and morphological effects of long duration space flight on the human central nervous system (CNS) and how current neuroimaging techniques may be utilized to study these effects. It must be determined if there will be any detrimental changes to the CNS from long term exposure to the space environment if human beings are to plan interplanetary missions or establish permanent space habitats. Research to date has focused primarily on the short term changes in the CNS as the result of space flight. The space environment has many factors such as weightlessness, electromagnetic fields, and radiation, that may impact upon the function and structure of the CNS. CNS changes known to occur during and after long term space flight include neurovestibular disturbances, cephalic fluid shifts, alterations in sensory perception, changes in proprioception, psychological disturbances, and cognitive changes. Animal studies have shown altered plasticity of the neural cytoarchitecture, decreased neuronal metabolism in the hypothalamus, and changes in neurotransmitter concentrations. Recent progress in the ability to study brain morphology, cerebral metabolism, and neurochemistry in vivo in the human brain would provide ample opportunity to investigate many of the changes that occur in the CNS as a result of space flight. These methods include positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI).

Single photon emission computed tomography in Alzheimer's disease and related disorders.

Alzheimer's disease and other dementia syndromes can be characterized by single photon emission computed tomography (SPECT). SPECT can be used to measure cerebral blood flow or neurotransmitter activity in these disorders. SPECT can help distinguish various neurologic disorders and also help elucidate their pathophysiologic processes. This article focuses on the use of SPECT in the study of Alzheimer's disease and related neurologic disorders.

Changes in the central nervous system and their clinical correlates during long-term spaceflight.

The purpose of this paper is to review the metabolic, neurotransmitter, and morphological changes that occur in the human central nervous system (CNS) during long-duration spaceflight. If there are to be either permanent space habitats or long-duration interplanetary missions, we must determine if there will be any detrimental reversible or irreversible effects on the brain from this prolonged exposure to space. We must also determine how these effects might manifest themselves in performance, psychological, or cognitive dysfunction. The space environment has many characteristics, including microgravity, electromagnetic fields, and radiation, that may have an effect on the function and morphology of the CNS. To date, the primary focus of U.S. research has been the changes that occur in the neurovestibular system in relation to space adaptation syndrome (particularly space motion sickness). Russia, which has more experience than the U.S. with spaceflights of durations longer than several weeks, has attempted to determine the consequences of this long-duration spaceflight on the human CNS. Changes already known to occur as a result of both short- and long-duration spaceflight include alterations in the neurovestibular system, cephalic fluid shifts, loss of total body fluid, changes in electrolyte concentrations, decreases in both muscular and skeletal mass, alterations in sensory perception, changes in proprioception, and changes in human behavior. This paper will examine how these effects are related to changes in cerebral metabolism, anatomy, and neurotransmitter physiology.

Quantitative analysis of PET and MRI data in normal aging and Alzheimer's disease: atrophy weighted total brain metabolism and absolute whole brain metabolism as reliable discriminators.

Average whole brain metabolic rates, when corrected for brain atrophy, are similar between patients with Alzheimer's disease (AD) and age-matched controls. To elucidate the relationship between reduced cognitive function and cerebral metabolism in patients with AD, we hypothesized that the absolute amount of glucose used by the entire brain may prove to be a more reliable indicator of the disease than metabolic rates calculated for a unit of brain weight. Twenty patients with the probable diagnosis of AD and 17 similarly aged controls underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) studies as well as magnetic resonance imaging (MRI) within a few days of each other. Average metabolic rates, when corrected for atrophy, were 3.91 +/- 1.02 and 4.43 +/- 0.87 (mg of glucose per 100 cc brain tissue per min +/- s.d.) respectively for AD patients and controls. Two other indices were determined, atrophy weighted total brain metabolism (calculated by multiplying the brain volume, determined by MR analysis, by the average metabolic rate) and absolute whole brain metabolism (calculated by multiplying the brain volume by the average metabolic rate corrected for atrophy). The former showed a very significant difference between the two groups (29.96 +/- 7.90 for AD patients compared to 39.1 +/- 7.0 for controls, p < 0.001). Atrophy weighted total brain metabolism also correlated very well with mini mental status exam (MMSE) scores (r = 0.59, p < 0.01). Absolute whole brain metabolism was significantly different between AD and control groups and correlated well with MMSE. These data demonstrate that although the metabolic rate per unit weight of the brain is unchanged in AD compared to controls, atrophy weighted total brain metabolism and absolute whole brain metabolism are significantly affected. Both indices may prove to be a sensitive correlate for cognitive dysfunction in AD.