Mapping the ischaemic penumbra with PET: a new approach.
Explore the source record for details and available documents.
Blood Flow Velocity↗
Biomedical subjects
J C Baron
Publications and source records attributed to J C Baron.
Relations between hypometabolism in the posterior association neocortex and hippocampal atrophy in Alzheimer's disease: a PET/MRI correlative study.
OBJECTIVES: Hippocampal atrophy and hypometabolism in the posterior association neocortex are two well known features of Alzheimer's disease. A correlation between these two features was reported twice previously, suggesting intriguing relations. This question has been reassessed, this time controlling for severity of dementia as well as assessing each side of the brain separately and using a voxel based image analysis in addition to the previously employed regions of interest (ROIs). PATIENTS AND METHODS: Eleven patients were studied with probable Alzheimer's disease and mild to moderate dementia in whom both volume MRI and PET assessed cerebral glucose consumption (CMRGlc) were available. Hypothesis driven correlations between hippocampal width (an index of atrophy) and CMRGlc were performed for two posterior association regions, the superior temporal and the inferior parietal (angular gyrus) cortices, using ROIs set separately for each hemisphere. To confirm significant correlations from the ROIs approach, if any, and to assess their specificity for the posterior association neocortex, CMRGlc image voxel based analysis of correlations with hippocampal width was then carried out. RESULTS: There was a significant correlation, in the positive-neurobiologically expected-direction, between right hippocampal width and right angular gyrus metabolism (p< 0.01, Spearman), which remained significant with Kendall partial correlation controlling for dementia severity (estimated by mini mental state scores). Statistical non-parametric mapping (SnPM) confirmed this correlation (p< 0.025), and showed a single additional correlation in the right middle temporal gyrus (p< 0.005), which is also part of the posterior association cortex. CONCLUSION: The findings with both ROIs and voxel based mapping replicate earlier reports of a relation between hippocampal atrophy and ipsilateral association cortex hypometabolism in Alzheimer's disease, and for the first time document that this relation is both region specific and independent of the dementing process itself. Why the correlation was significant only for the right hemisphere is unclear but may be related to the limited sample. Hippocampal-neocortical disconnection due to early and severe medial temporal lobe pathology may at least partly explain the posterior association cortex hypometabolism found in Alzheimer's disease.
Aged↗
Perfusion thresholds in human cerebral ischemia: historical perspective and therapeutic implications.
After middle cerebral artery occlusion (MCAO) in the laboratory animal, the ischemic penumbra has been documented as a severely hypoperfused, functionally impaired, but still viable cortex which can regain its function and escape infarction if it is reperfused before a certain time has elapsed. The penumbra surrounds the ischemic core of already irreversibly damaged tissue, and is progressively recruited into the core with increasing MCAO duration. In the animal, the threshold of cerebral blood flow (CBF) below which neuronal function is impaired and the tissue is at risk of infarction is around 22 ml/100 g/min (approximately 40% of normal) in the awake or lightly anesthetized monkey, and around 30--35 ml/100 g/min in the cat and the rat. The threshold of CBF below which the tissue becomes irreversibly damaged and will progress to infarction depends on the duration of ischemia, and is around 10 ml/100 g/min for 1--2 h (approximately 20% of normal) and around 18 ml/100 g/min for permanent ischemia in the monkey. Mildly reduced CBF down to the 40% threshold (termed 'oligemia') is normally well tolerated, and the affected tissue is not at risk of infarction under uncomplicated conditions (in the animal, however, selective neuronal death may occur even with only mildly reduced CBF values, but this sequela of stroke seems an exceptional encounter in man). Classic studies with carotid artery clamping in man have provided estimates for the penumbra threshold at around 20 ml/ 100 g/min for the whole brain, but only recently have imaging studies allowed to document the existence of the penumbra in acute stroke and given estimates of local CBF thresholds. With PET, the penumbra is characterized by a reduced CBF, an increased oxygen extraction fraction, and a relatively preserved oxygen consumption (CMRO(2)). In a series of PET studies performed 5--18 h after stroke onset, we have determined the threshold for penumbra to be around 20 ml/100 g/min, and documented that the extent of neurological recovery is proportional to the volume of penumbra that eventually escaped infarction. Within this time interval, the thresholds for irreversible damage were around 8 ml/ 100 g/min for CBF and around 0.9 ml/100 g/min for CMRO(2). Recent studies with diffusion-weighted and perfusion MR have reported similar relative thresholds for CBF of about 50 and 18% for penumbra and core, respectively. Although it is likely that the threshold for irreversibility will be lower with shorter duration since clinical onset, this has not been documented thus far. Because saving the penumbra will improve clinical outcome, it should constitute the main target of acute stroke therapy. We found evidence of penumbra in about one third of the cases studied between 5 and 18 h after onset, and as late as 16 h after symptom onset in occasional patients, suggesting the therapeutic window may be protracted in at least a fraction of the cases; similar experience has recently accrued from diffusion-weighted MR and perfusion MR. In the remaining patients, there was evidence of early extensive damage or early spontaneous reperfusion, which would make them inappropriate candidates for neuroprotective therapy. Recent evidence from PET studies of relative perfusion performed within 3 h of onset suggests that early thrombolysis indeed saves the tissue with CBF below a critical threshold of 12 ml/ 100 g/min, with a correlation between the volume of such tissue escaping infarction and subsequent neurological recovery. Thus, mapping the penumbra in the individual patient with physiologic imaging should allow to formulate a pathophysiological diagnosis, and in turn to design a rational management of the stroke patient and to increase the sensitivity of drug trials by appropriate patient selection.
Animals↗
Effects of age on brain activation during auditory-cued thumb-to-index opposition: A positron emission tomography study.
BACKGROUND AND PURPOSE: Available data indicate a decline in fine finger movements with aging, suggesting changes in central motor processes. Thus far no functional neuroimaging study has assessed the effect of age on activation patterns during finger movement. METHODS: We used high-resolution perfusion positron emission tomography to study 2 groups of 7 healthy right-handed subjects each: a young group (mean age, 24 years) and an old group (mean age, 60 years). The task was a thumb-to-index tapping, auditory-cued at 1. 26 Hz with a metronome, with either the right or the left hand. The control condition was a resting state with the metronome on. RESULTS: Significant differences between old and young subjects were found, suggesting significant overactivation in older subjects affecting the superior frontal cortex (premotor-prefrontal junction) ipsilateral to the moving fingers, as if the execution of this apparently simple motor task was judged more complex by the aged brain. Similar findings in previous perceptual and cognitive paradigms have been interpreted as a compensation process for the neurobiological changes of aging. Analysis of the control condition data in our sample showed, however, that this prefrontal overactivation in the old group was due at least in part to higher resting perfusion in anterior brain areas in the young subjects. CONCLUSIONS: The changes in brain function observed in this study may underlie the subtle decline in fine motor functions known to occur with normal aging. Our findings emphasize the importance of using an age-matched control group in functional imaging studies of motor recovery after stroke.
Acoustic Stimulation↗
Dynamics of motor network overactivation after striatocapsular stroke: a longitudinal PET study using a fixed-performance paradigm.
BACKGROUND AND PURPOSE: Although excessive brain activation during affected hand motion after stroke is well documented, its time course has been rarely studied, and when studied, this has either been with passive movement or with active but cognitively complex task and uncontrolled performance over time, complicating interpretation. METHODS: According to a prospective and longitudinal design, we studied 5 right-handed patients with right-sided hemiparesis due to first-ever left striatocapsular infarction. Three-dimensional PET H(2)O(15) studies were performed twice ( approximately 7 and approximately 31 weeks after stroke [PET1 and PET2, respectively]) during right thumb-to-index tapping executed at the same rate in both studies (1.26 Hz, auditory cued). With SPM96 software, significant group and individual overactivations (P<0.05, corrected for multiple comparisons) were computed by comparison with a group of 7 healthy age-matched right-handed control subjects performing the same task. RESULTS: Motor recovery was significant from PET1 to PET2. Both the group and individual analyses revealed striking overactivations at PET1, affecting notably the cortical hand area and the whole motor network bilaterally. These overactivations were less prominent at PET2 over both hemispheres, not only in terms of Z score but also in terms of spatial extent (almost reaching statistical significance in the affected hemisphere for the latter, P=0.09). However, new overactivations were found at PET2 in the left prefrontal areas, the putamen, and the premotor cortex. CONCLUSIONS: This study is the first to document that to perform the same simple movement of the paretic fingers, the brain with subcortical infarction shows less overactivations at the late than at the early timepoint, especially on the affected side, suggesting reduced recruitment of affected-hemisphere motor networks. However, unaffected-hemisphere prefrontal, premotor, and putaminal overactivations, observed at PET2 only, may suggest late-appearing compensatory reorganization.
Aged↗
[Contribution of positron emission tomography to functional neuroimaging in Alzheimer's disease].
When combined with cognitive investigations, functional neuroimaging methods such as positron emission tomography allow to depict the neural substrates that underlie the neuropsychological alterations in Alzheimer's disease. Capitalising on the variance in both cognitive performances and resting cerebral metabolic rate of glucose (CMRGlc) in Alzheimer's disease, it is possible to correlate these two quantitative variables on a pixel-by-pixel basis and to generate maps showing the significant correlations in stereotaxic space. Some examples using this approach in the domain of memory disorders are presented in this brief review. We notably show that the localisation of the significant correlations differs from one memory system to another, as evaluated by clinical memory tasks. This approach also unravels the compensatory mechanisms that take place with evolution of the disease. Over and above its interest in clinical neuropsychology, this method constitutes a new source of inferences complementary to the classic activation paradigm in normal subjects, as the latter identifies the cerebral structures that are involved with, but not necessarily indispensable for, the normal execution of the task. This approach highlights the interest of combining functional neuroimaging and neuropsychology to better understand the neural substrates of cognitive deficits in both patients with memory disorders and elderly normal subjects.
Alzheimer Disease↗
[Recommendations for the creation of neuro-vascular units].
Explore the source record for details and available documents.
Brain Ischemia↗
Familial occipital calcifications, hemorrhagic strokes, leukoencephalopathy, dementia, and external carotid dysplasia.
OBJECTIVE: To describe a new familial association of late-onset dementia, patchy leukoencephalopathy, intracerebral hemorrhages, bilateral occipital calcifications (BOC), and external carotid artery dysplasia (ECAD). METHODS: At age 62, the proband, who was of Spanish descent, had left temporal hemorrhage in a background of progressive mental deterioration. Neuroimaging revealed fine tram-line BOC, extensive leukoencephalopathy, and bilateral ECAD. Biologic screening for celiac disease was negative. Skin biopsy with ultrastructural study revealed heretofore unreported changes in the basal lamina of capillaries, with multilayered appearance and round-shaped microcalcifications. Of 19 next-of-kin who survived beyond 60 years of age, six had brain disorders; four of the six presented at least three components of the syndrome. The proband's mother had died at age 83 with profound dementia; one sister, who was diagnosed with dementia with BOC and leukoencephalopathy at age 67, died 2 years later from intracerebral hemorrhage; a brother had an occipital hemorrhage at age 58, at which time BOC and leukoencephalopathy were discovered; and another brother died after a minor stroke at age 70 with dementia, leukoaraiosis, BOC, and ECAD. A proband's cousin also had an unexplained ischemic stroke at age 55, but without other features of the entity. In no subject was there evidence of seizures, facial angioma, or intracranial vascular malformation, and arterial hypertension was neither constant nor severe. CONCLUSION: These clinical, neuroradiologic, and histologic features suggest a new familial cerebrovascular entity with widespread microvascular calcifications and autosomal (presumably dominant) inheritance. We suggest the acronym FOCHS-LADD, for familial occipital calcifications, hemorrhagic strokes, leukoencephalopathy, arterial dysplasia, and dementia.
Aged↗
Functional neuroanatomy of amnesia: positron emission tomography studies.
In this article, we review the principles of, and provide examples for, the new approach of functional neuropsychology in the field of amnesia. In the permanent amnesic syndrome, positron emission tomography (PET) can provide statistical maps of the brain regions with significantly impaired resting metabolism in comparison with control subjects. These regions include not only Papez's circuit but also the left supramarginal gyrus, which may explain in part the retrograde amnesia present in most cases of amnesic syndrome. This approach is also of great interest in transient global amnesia (TGA) because the defect of episodic memory is highly selective and occurs without permanent damage. The few available PET studies in TGA suggest the dysfunction of a distributed network including the hippocampal region and the prefrontal cortex, with a different pattern individually. Further studies will be necessary to better understand the relationships between the precise cognitive deficits in TGA and the pattern of brain hypometabolism. In Alzheimer's disease (AD), the study of the correlations between memory test scores and metabolic values across a sample of subjects provides a map of those brain structures whose synaptic pathology dysfunction underlies the particular neuropsychological alteration. The distribution of the sites of correlations shows striking differences according to each memory system. This approach should open the way for the unravelling of the neurobiological substrates of both cognitive impairment and compensatory mechanisms in neurodegenerative diseases. Over and above their applications in neurological research, such studies in brain-diseased subjects are particularly useful for establishing cognitive and neurobiological models of human memory, because they allow the highlighting of the neural networks that are essential for memory function. From a cognitive neuroscience perspective, the functional neuropsychology of amnesia is, therefore, complementary to the classic activation paradigm in normal subjects, which identifies the cerebral structures that are involved with, but not necessarily indispensable for, the execution of the task.
Alzheimer Disease↗
Use of the radial forearm fasciocutaneous free flap and montgomery salivary bypass tube for pharyngoesophageal reconstruction.
BACKGROUND: Head and neck reconstructive surgeons involved in pharyngoesophageal reconstruction have several options available to repair the defect after partial or total laryngopharyngectomy. There is no uniform agreement among head and neck surgeons as to which of the most frequently used techniques offers the best results. METHODS: A retrospective study was performed on 20 consecutive patients who had undergone reconstruction of the hypopharynx and cervical esophagus using a radial forearm free flap with Montgomery salivary bypass tube at the Massachusetts Eye and Ear Infirmary in Boston, Massachusetts, and St. Louis University, Department of Otolaryngology-Head and Neck Surgery between 1992 and 1996. This reconstruction was used for primary reconstruction after total or partial laryngopharyngectomy with cervical esophagectomy, partial pharyngectomy sparing the larynx, and for reconstruction of the stenotic neopharynx after laryngectomy. RESULTS: The overall rate of pharyngocutaneous fistula was 20%, and the rate of postoperative stricture was 10%. Of patients reconstructed with this technique, 85% were able to resume oral alimentation, whereas 15% remained G-tube dependent. Of the 18 patients who did not have their larynges remain intact, 6 were able to develop useful tracheoesophageal speech. CONCLUSIONS: The results of this study show that the radial forearm fasciocutaneous free flap in combination with the Montgomery salivary bypass tube is extremely useful for reconstruction of partial and circumferential defects of the hypopharynx and cervical esophagus.
Adult↗
Mapping the visual recognition memory network with PET in the behaving baboon.
By means of a novel 18F-fluoro-deoxyglucose PET method designed for cognitive activation imaging in the baboon, the large-scale neural network involved in visual recognition memory in the nonhuman primate was mapped for the first time. In this method, the tracer is injected in the awake, unanesthetized, and unrestrained baboon performing the memory task, and brain imaging is performed later under light anesthesia. Brain maps obtained during a computerized trialunique delayed matching-to-sample task (lists of meaningless geometrical patterns and delay > 9 seconds) were statistically compared pixel-by-pixel to maps obtained during a specially designed visuomotor control task. When displayed onto the baboon's own anatomic magnetic resonance images, foci of significant activation were distributed along the ventral occipitotemporal pathway, the inferomedial temporal lobe (especially the perirhinal cortex and posterior hippocampal region), and the orbitofrontal cortex, consistent with lesion, single-unit, and autoradiographic studies in monkeys, as well as with activation studies in healthy humans. Additional activated regions included the nucleus basalis of Meynert, the globus pallidus and the putamen. The results also document an unexpected left-sided advantage, suggesting hemispheric functional specialization for recognition of figural material in nonhuman primates.
Animals↗
Which targets are relevant for therapy of acute ischemic stroke?
Explore the source record for details and available documents.
Acute Disease↗
[Recommendations for the use of intravenous thrombolytic therapy in cerebrovascular ischemic accident. French Society of Neurovascular Disorders].
Explore the source record for details and available documents.
Brain Ischemia↗
[The pathophysiology of migraine: insights from functional neuroimaging].
Over the last 20 years, functional neuroimaging has led to major advances in the understanding of the pathophysiology of migraine. The migraine aura is characterized by the occurrence of an hypoperfusion of moderate intensity which is peculiar by its initial appearance in the posterior cortex and its anterior spread at a speed of about 2 to 3mm per minute, congruent with the migrainous march of neurologic deficit and reminiscent of the phenomenon of cortical spreading depression described in the laboratory animal after various neuronal aggressions. The hypoperfusion is followed by a phase of long-lasting hyperperfusion temporally dissociated from the headache, which seems rather to result from vasodilatation and inflammation of the extra-cerebral large vessels. Although this sequence of hypoperfusion followed by hyperperfusion would be consistent with an ischemic process, there is presently no formal argument in favour of such a process being operational in migraine aura. It is however possible that migrainous subjects are genetically susceptible to the development of some unknown process at the borderline between spreading depression and classic ischemia. In migraine without aura, the data indicate only rare and mild changes in brain perfusion, although there also exist isolated observations of pauci-symptomatic spreading bilateral hypoperfusion. Physiologic imaging has also documented the occurrence during migraine without aura of a dorsal mesencephalic activation in the vicinity of the raphé and the locus coeruleus, independent of the pain itself and which might represent the long sought-after "migraine generator". It remains unknown if this phenomenon is also present in migraine with aura. The main prevalent hypotheses attempting a synthesis of all the available data are briefly presented in the conclusion.
Brain↗
[Function imaging of the hippocampus in Korsakoff's syndrome].
A case of alcoholic Korsakoff syndrome is reported in a 47 year-old-man. Neuropsychological examination revealed an important both anterograd and retrograd amnesia but procedural and short-term memory were not affected nor was intellectual capacity. Cerebral IRM was normal. Pet scan demonstrated a previously unsuspected fact: the diminution of glucose metabolism in the two hippocampus and in the mamillary bodies.
Hippocampus↗
Relationships between striatal dopamine denervation and frontal executive tests in Parkinson's disease.
Indirect evidence from human and monkey investigations supports the idea that impaired frontal tasks in Parkinson's disease (PD) may result from striato-frontal disruption caused by dopamine (DA) denervation of the caudate nucleus. To directly investigate this hypothesis, we used PET with 11C-S-Nomifensine (11C-S-NMF), a sensitive marker of striatal DA denervation, in 10 non-demented PD patients in whom two frontal executive tests, the object alternation (OA) and the conditional associative learning (CAL) tasks, thought to reflect mainly set-shifting/inhibition and planning, respectively, were given. In addition, the central executive function of verbal working memory was assessed with the Brown Peterson paradigm (BPP). We found a highly significant correlation between right caudate 11C-S-NMF specific binding and OA performance, less significant and reverse-direction correlations between CAL performance and putamen 11C-S-NMF binding, and no significant correlation with BPP performance. Thus, caudate DA denervation may subtend poor set-shifting/inhibition process in PD. Our results also point to distinct and complex relationships between striatal DA and specific frontal tasks.
Adult↗
Combined use of T1-weighted MRI and MRA for stereotaxic lesioning of the nonhuman primate brain: application to the rhinal cortex.
Stereotaxic brain lesioning is widely used to develop experimental models of human brain disease in the nonhuman primate. To avoid intraoperative vascular complications such as intracranial hemorrhage, we developed a methodology that is easy to implement. This method combines T1-weighted magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). This technique is applied to produce bilateral neurotoxic lesions of the rhinal cortex, a structure located medially in the temporal lobe, in eight baboons (including five sham-operated animals with needle descents but no ibotenic acid injection). Two other baboons were lesioned before the MRA technology was available. The MRA sequence (two-dimensional time-of-flight, axial acquisition) was used to localize the blood vessels in the needle trajectories, i.e., the highly vascularized sylvian fissure and temporal gyri. The vessel coordinates were transposed onto the coronal MRI-TI images, onto which the injection sites were determined and the planned needle tracks drawn. In the eight baboons that had MRA, 26.8% of these needle tracks had to be slightly displaced because of the presence of blood vessels. The stereotaxic coordinates of the final target sites were then calculated with respect to six skull landmarks that also served as a reference during surgery. No intracranial hemorrhage occurred in any of the eight baboons in which MRA was performed, in contrast to one of the two baboons not studied with MRA. The histological analysis showed a good extent of the rhinal lesions in all lesioned animals, with minimal damage to areas other than those that were targeted. Thus, combined use of MRI-TI and MRA proved to be reliable in reducing vascular complications, affording new advances for stereotaxic surgery in nonhuman primates.
Animals↗
Emission tomography contribution to clinical neurology.
The role of functional neuroimaging techniques in furthering the understanding of pathophysiological mechanisms of neurological diseases and in the assessment of neurological patients is increasingly important. Here, we review data mainly from emission tomography techniques, namely positron emission tomography (PET) and single photon emission computerized tomography (SPECT), that have helped elucidate the pathophysiology of a number of neurological diseases and have suggested strategies in the treatment of neurological patients. We also suggest possible future developments of functional neuroimaging applied to clinical populations and briefly touch on the emerging role of functional magnetic resonance imaging (fMRI) in clinical neurology and neurosurgery.
Brain↗