Biomedical subjects

Tim D Fryer

Publications and source records attributed to Tim D Fryer.

28 records · Page 2Linked to original sources

PubMed2004

Incidence and mechanisms of cerebral ischemia in early clinical head injury.

Antemortem demonstration of ischemia has proved elusive in head injury because regional CBF reductions may represent hypoperfusion appropriately coupled to hypometabolism. Fifteen patients underwent positron emission tomography within 24 hours of head injury to map cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), and oxygen extraction fraction (OEF). We estimated the volume of ischemic brain (IBV) and used the standard deviation of the OEF distribution to estimate the efficiency of coupling between CBF and CMRO2. The IBV in patients was significantly higher than controls (67 +/- 69 vs. 2 +/- 3 mL; P < 0.01). The coexistence of relative ischemia and hyperemia in some patients implies mismatching of perfusion to oxygen use. Whereas the saturation of jugular bulb blood (SjO2) correlated with the IBV (r = 0.8, P < 0.01), SjO2 values of 50% were only achieved at an IBV of 170 +/- 63 mL (mean +/- 95% CI), which equates to 13 +/- 5% of the brain. Increases in IBV correlated with a poor Glasgow Outcome Score 6 months after injury (rho = -0.6, P < 0.05). These results suggest significant ischemia within the first day after head injury. The ischemic burden represented by this "traumatic penumbra" is poorly detected by bedside clinical monitors and has significant associations with outcome.

Adolescent↗

PubMed2004

Does the acute diffusion-weighted imaging lesion represent penumbra as well as core? A combined quantitative PET/MRI voxel-based study.

In acute ischemic stroke, the diffusion-weighted imaging (DWI) lesion is widely held to represent the core of irreversible damage and is therefore crucial in selecting patients for thrombolysis. However, recent research suggests it may also represent penumbra. An illustrative patient was imaged 7 hours after stroke onset with back-to-back 3T diffusion tensor imaging and quantitative positron emission tomography, which showed a DWI lesion and misery perfusion, respectively. Using previously validated voxel-based probabilistic CBF, CMRO2, and Oxygen Extraction Fraction (OEF) thresholds, the authors show that the DWI lesion contained not only core but also substantial proportions of penumbra. Also, severe apparent diffusion coefficient reductions were present within the potentially salvageable penumbra as well as in the core. These findings have potential implications regarding treatment decisions.

Brain Ischemia↗

PubMed2003

Assessment of cerebrovascular autoregulation in head-injured patients: a validation study.

BACKGROUND AND PURPOSE: Cerebrovascular autoregulation is frequently measured in head-injured patients. We attempted to validate 4 bedside methods used for assessment of autoregulation. METHODS: PET was performed at a cerebral perfusion pressure (CPP) of 70 and 90 mm Hg in 20 patients. Cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo2) were determined at each CPP level. Patients were sedated with propofol and fentanyl. Norepinephrine was used to control CPP. During PET scanning, transcranial Doppler (TCD) flow velocity in the middle cerebral artery was monitored, and the arterio-jugular oxygen content difference (AJDo2) was measured at each CPP. Autoregulation was determined as the static rate of autoregulation based on PET (SROR(PET)) and TCD (SROR(TCD)) data, based on changes in AJDo2, and with 2 indexes based on the relationship between slow waves of CPP and flow velocity (mean velocity index, Mx) and between arterial blood pressure and intracranial pressure (pressure reactivity index, PRx) RESULTS: We found significant correlations between SROR(PET) and SROR(TCD) (r2=0.32; P<0.01) and between SROR(PET) and PRx (r2=0.31; P<0.05). There were no significant associations between PET data and autoregulation as assessed by changes in AJDo2. Global CMRo2 was significantly lower at the higher CPP (P<0.01). CONCLUSIONS: Despite some variability, SROR(TCD) and PRx may provide useful approximations of autoregulation in head-injured patients. At least with our methods, CMRo2 changes with the increase in CPP; hence, flow-metabolism coupling may affect the results of autoregulation testing.

Adolescent↗

PubMed2003

Progressive non-fluent aphasia is associated with hypometabolism centred on the left anterior insula.

Progressive non-fluent aphasia (PNFA) is a syndrome in which patients lose the ability to communicate fluently in the context of relative preservation of single word comprehension and non-linguistic cognitive abilities. Neuroimaging in case studies with PNFA has failed to identify a consistent neural substrate for the language disorder. In this study of a group of patients (n=10) whose presenting complaint was progressive dysfluency, resting cerebral metabolism was measured using [18F]fluorodeoxyglucose-PET and analysed with the technique of statistical parametric mapping (SPM). Regional atrophy was assessed with voxel-based morphometry (VBM). Seven patients had a 'pure' PNFA syndrome, while the remaining three had additional features of a more pervasive dementia. Compared with controls, the patients showed hypometabolism in several regions that, most notably, included the left anterior insula/frontal opercular region. The VBM analysis revealed only one small area of atrophy in the left peri-Sylvian region. Analysis of the pure PNFA cases (n=7) relative to controls yielded qualitatively similar results to those of the whole group, suggesting that these cases were also at risk of a more generalized dementia, a finding borne out in subsequent follow-up of two cases to date. The PNFA group was then compared with a group with Alzheimer's disease (n=10) whose clinical profile did not include non-fluent aphasic features. In this analysis, the only persisting hypometabolic region was that centred over the left anterior insula. VBM did not identify any regional differences in atrophy between PNFA and Alzheimer's disease. In the light of current theories of fluent language production, the findings offer anatomical evidence that the breakdown in fluency is due to a motor articulatory planning deficit (speech apraxia) combined with a variable degree of agrammatism.

Aged↗

PubMed2003

Limbic hypometabolism in Alzheimer's disease and mild cognitive impairment.

The neural basis of the amnesia characterizing early Alzheimer's disease (AD) remains uncertain. Postmortem pathological studies have suggested early involvement of the mesial temporal lobe, whereas in vivo metabolic studies have shown hypometabolism of the posterior cingulate cortex. Using a technique that combined the anatomic precision of magnetic resonance imaging with positron emission tomography, we found severe reductions of metabolism throughout a network of limbic structures (the hippocampal complex, medial thalamus, mamillary bodies, and posterior cingulate) in patients with mild AD. We then studied a cohort with mild cognitive impairment in whom amnesia was the only cognitive abnormality and found comparable hypometabolism through the same network. The AD and mild cognitive impairment groups were differentiated, however, by changes outside this network, the former showing significant hypometabolism in amygdala and temporoparietal and frontal association cortex, whereas the latter did not. The amnesia of very early AD reflects severe but localized limbic dysfunction.

Alzheimer Disease↗

PubMed2003

Responses of posttraumatic pericontusional cerebral blood flow and blood volume to an increase in cerebral perfusion pressure.

In and around traumatic contusions, cerebral blood flow (CBF) is often near or below the threshold for ischemia. Increasing cerebral perfusion pressure (CPP) in patients with head injuries may improve CBF in these regions. However, the pericontusional response to this intervention has not been studied. Using positron emission tomography (PET), we have quantified the response to an increase in CPP in and around contusions in 18 contusions in 18 patients. Regional CBF and cerebral blood volume (CBV) were measured with PET at CPPs of 70 and 90 mmHg using norepinephrine to control CPP. Based upon computed tomography, regions of interest (ROIs) were placed as two concentric ellipsoids, each of 1-cm width, around the core of the contusions. Measurements were compared with a control ROI in tissue with normal anatomic appearance. Baseline CBF and CBV increased significantly with increasing distance from the core of the lesion. The increase in CPP led to small increases in CBF in all ROIs except the core. The largest absolute CBF increase was found in the control ROI. Relative CBF increases did not differ between ROIs so that ischemic areas remained ischemic. Pericontusional oedema on computed tomography was associated with lower absolute values of CBF and CBV but did not differ from nonoedematous tissue in the relative response to CPP elevation.

Adolescent↗

PubMed2002

(18)F-Endothelin-1, a positron emission tomography (PET) radioligand for the endothelin receptor system: radiosynthesis and in vivo imaging using microPET.

Positron emission tomography (PET) is a powerful technique with the sensitivity to image and quantify receptor-bound radioligands in vivo. Recent progress in PET scanner technology has resulted in the development of dedicated tomographs designed for small animals, with resolution that allows the delineation of discrete organs and their larger substructures in rats and mice. Our aim was to determine whether endothelin-1 (ET-1) could be labelled with (18)F, and whether the resulting (18)F-ET-1 would have the required pharmacokinetic properties to permit binding and imaging of ET receptors in vivo. (18)F-ET-1 could be produced in a total radiochemical yield of 5.9+/-0.7% in 207+/-3 min (n=20). Specific radioactivities were in the range 220-370 GBq/micromol, and the radiochemical purity of the isolated (18)F-ET-1 was >95%. In vivo distribution in the rat was studied using microPET. High levels of (18)F-ET-1 uptake were found in lung and kidney, whereas liver showed moderate levels of uptake. The resolution of the microPET scanner was sufficient to differentiate heterogeneous uptake in subrenal structures in the rat.

Animals↗

PubMed2002

Effect of hyperventilation on cerebral blood flow in traumatic head injury: clinical relevance and monitoring correlates.

OBJECTIVE: To investigate the effect of hyperventilation on cerebral blood flow in traumatic brain injury. DESIGN: A prospective interventional study. SETTING: A specialist neurocritical care unit. PATIENTS: Fourteen healthy volunteers and 33 patients within 7 days of closed head injury. INTERVENTIONS: All subjects underwent positron emission tomography imaging of cerebral blood flow. In patients, PaCO2 was reduced from 36 +/- 1 to 29 +/- 1 torr (4.8 +/- 0.1 to 3.9 +/- 0.1 kPa) and measurements repeated. Jugular venous saturation (SjvO2 ) and arteriovenous oxygen content differences (AVDO2 ) were monitored in 25 patients and values related to positron emission tomography variables. MEASUREMENTS AND MAIN RESULTS: The volumes of critically hypoperfused and hyperperfused brain (HypoBV and HyperBV, in milliliters) were calculated based on thresholds of 10 and 55 mL.100g(-1).min(-1), respectively. Whereas baseline HypoBV was significantly higher in patients ( p<.05), baseline HyperBV was similar to values in healthy volunteers. Hyperventilation resulted in increases in cerebral perfusion pressure (p <.0001) and reductions in intracranial pressure (p <.001), whereas SjvO2 (>50%) and AVDO2 (<9 mL/mL) did not exceed global ischemic thresholds. However, despite these beneficial effects, hyperventilation shifted the cerebral blood flow distribution curve toward the hypoperfused range, with a decrease in global cerebral blood flow (31 +/- 1 to 23 +/- 1 mL.100g(-1).min(-1); p<.0001) and an increase in HypoBV (22 [1-141] to 51 [2-428] mL; p<.0001). Hyperventilation-induced increases in HypoBV were apparently nonlinear, with a threshold value between 34 and 38 torr (4.5-5 kPa). CONCLUSIONS: Hyperventilation increases the volume of severely hypoperfused tissue within the injured brain, despite improvements in cerebral perfusion pressure and intracranial pressure. Significant hyperperfusion is uncommon, even at a time when conventional clinical management includes a role for modest hyperventilation. These reductions in regional cerebral perfusion are not associated with ischemia, as defined by global monitors of oxygenation, but may represent regions of potentially ischemic brain tissue.

Adolescent↗

PubMed2002

A case study of hemispatial neglect using finite element analysis and positron emission tomography.

BACKGROUND: The authors present a patient who developed transient hemispatial neglect following surgical drainage of a large right frontotemporal arachnoid cyst. As symptoms evolved in parallel with brain shift over the subsequent months, the authors hypothesized that the disorder was associated with the appearance of mechanical stresses in the cerebral mantle. METHODS: To map tissue stress at the various stages of deformation, a finite element computer simulation was conducted on the basis of computed tomography scans of the patient. RESULTS: The authors' results demonstrate substantial shear and compressive stress concentrations in the parietal lobe, a region commonly associated with neglect, and where positron emission tomography confirmed hypoperfusion in this patient. Treatment with combined ventricular-peritoneal and cystoperitoneal shunts was accompanied by clinical recovery and improvement of right parietal lobe cerebral blood flow. CONCLUSIONS: The authors conclude that brain deformation was a contributing factor in the reversible neglect syndrome by compromising the normal flow of blood and/or the deactivation of subcortical circuits of the parietal lobe.

Aged↗

PubMedDate not supplied

Targeting the vulnerable plaque: the evolving role of nuclear imaging.

The majority of acute ischemic events relating to atherosclerosis are caused by plaque rupture and ensuing thrombosis. The risk of plaque rupture is dictated in part by plaque morphology, which in turn is influenced by pathophysiologic mechanisms at the cellular and molecular level. Anatomic imaging modalities such as intravascular ultrasound, high-resolution magnetic resonance imaging, and multislice computed tomography can identify morphologic features of the vulnerable plaque, such as a large lipid core and thin fibrous cap, but give little or no information regarding molecular and cellular mechanisms, such as endothelial function, macrophage activation, lipid transport and metabolism, and cell death. Recent studies suggest that nuclear imaging may be able to provide images of sufficient quality to identify and quantify some of these molecular and cellular pathophysiologic processes. In the future this could allow for the early identification and noninvasive monitoring of vulnerable plaque.

Animals↗