Biomedical subjects

C Svarer

Publications and source records attributed to C Svarer.

13 recordsLinked to original sources

PubMed2001

Correlations of brain MRI parameters to disability in multiple sclerosis.

OBJECTIVES: The objective was to correlate magnetic resonance imaging (MRI) T2-weighted lesion load and measures of white matter atrophy in the brain to disability in a population-based sample of patients with multiple sclerosis (MS). MATERIAL AND METHODS: A well defined cohort of patients was drawn at random from the general MS population by using the Danish Multiple Sclerosis Registry. A semi-automated local thresholding technique was used to quantify T2-weighted lesions on MRI; whereas manual tracing was applied to measure the corpus callosum brain ratio (CCR) and the ventricle brain ratio (VBR). RESULTS: A sample of 86 patients with a mean age of 43.3 years (SD 4.3), mean disease duration of 13.6 years (SD 4.4) and a median Expanded Disability Status Score (EDSS) of 6.0 was identified. The correlation between total lesion area of the brain (TLA) and disability (EDSS) for the whole sample was moderate (Spearman rank correlation coefficient r=0.48, P<0.001). Also correlations of CCR and VBR to disability (r=0.32-0.46) were significant. CONCLUSIONS: Correlations of TLA and disability in this study were rather strong. Hence, T2-weighted MRI lesion load in the brain still plays an important role as a surrogate marker of disease and as a secondary outcome measure in phase III treatment trials.

Adult↗

PubMed2001

The (18)F-fluorodeoxyglucose lumped constant determined in human brain from extraction fractions of (18)F-fluorodeoxyglucose and glucose.

Quantification of regional cerebral glucose metabolism (CMRglc) using positron emission tomography and 18F-fluorodeoxyglucose (PET-FDG) requires knowledge of the correction factor between FDG and glucose net clearance, the FDG lumped constant (LC). Because diverging values for LC have been obtained, the authors reevaluated LC by measuring the ratio of the cerebral net extraction fractions of FDG (E*) and glucose (E) from arteriovenous cerebral measurements. Thirty subjects were studied (mean age = 25 +/- 4 years): 12 during a programed infusion of FDG and 18 after a bolus injection of FDG. In the infusion study, LC was calculated as the ratio E*/E. In the bolus study, E* was calculated from the slope of a Patlak-Gjedde plot. Lumped constant was significantly smaller in the infusion study as compared with the bolus study (0.48 +/- 0.16 vs. 0.81 +/- 0.27, P < 0.001). In 4 subjects studied during continuous FDG infusion for 2.5 hours, LC decreased to 0.36 +/- 0.11. These results suggest that the "steady-state" method underestimates LC because E* continues to decline because of significant labeled product. Further, the authors provide evidence for resetting of LC toward a greater value. The subsequent resetting of CMRglc provides a physiologically more meaningful estimate and allows for comparison of CMRglc values between different methodologies.

Brain↗

PubMed2000

Cerebral activation during micturition in normal men.

Specific cerebral lesions have shown the crucial role of the brain in the control of micturition. The precise identification of the anatomical cerebral structures involved in micturition can contribute to a better understanding of the control of micturition and the development of therapeutic models. Various neuropathological and animal studies have referred to the medulla oblongata, pons, limbic system, superior frontal lobe and premotor cortical regions as areas implicated in micturition control. The aim of this study was to investigate whether the activity of these areas during micturition can be confirmed by PET in normal men. The distribution of the regional cerebral blood flow after bolus injection of (15)O water was used as an indirect measure of cerebral activation. PET scans were performed during the following three conditions: (i) at rest with the bladder empty; (ii) during simulated micturition after instillation of isotonic saline into the urinary bladder; and (iii) the withholding of urine (saline). Normal micturition using this model was achieved in eight out of 12 right-handed normal subjects. The changes in bladder contraction, bladder pressure and intra-abdominal pressure were monitored on-line during the whole scanning session by a cystometry device. The images were analysed using statistical parametric mapping at a significance threshold of P < 0.05 with correction for multiple independent comparisons. Micturition versus rest was associated with bilateral activation of areas close to the postcentral gyrus, inferior frontal gyrus, globus pallidus, cortex cerebelli, vermis and midbrain. On the left side, activation of the middle frontal gyrus, superior frontal gyrus, superior precentral gyrus, thalamus and the caudal part of the anterior cingulate gyrus was seen, while on the right side we found activation in the supramarginal gyrus, mesencephalon and insula. When the threshold value was lowered to P < 0.001 (Z > 3.09) without correction for multiple comparisons, we found additional activation in the medial pontine tegmentum, mesencephalon, right thalamus, right middle frontal gyrus and left insula. When urine- withholding was compared with rest, the left insula showed a tendency to activate. We conclude from this study, in which urinary bladder contraction was verified cystometrically, that the onset and maintenance of micturition in normal men is associated with a vast network of cortical and subcortical regions, confirming observations from clinical and animal studies.

Adult↗

PubMed2000

Quantitation of regional cerebral blood flow corrected for partial volume effect using O-15 water and PET: I. Theory, error analysis, and stereologic comparison.

Limited spatial resolution of positron emission tomography (PET) can cause significant underestimation in the observed regional radioactivity concentration (so-called partial volume effect or PVE) resulting in systematic errors in estimating quantitative physiologic parameters. The authors have formulated four mathematical models that describe the dynamic behavior of a freely diffusible tracer (H215O) in a region of interest (ROI) incorporating estimates of regional tissue flow that are independent of PVE. The current study was intended to evaluate the feasibility of these models and to establish a methodology to accurately quantify regional cerebral blood flow (CBF) corrected for PVE in cortical gray matter regions. Five monkeys were studied with PET after IV H2(15)O two times (n = 3) or three times (n = 2) in a row. Two ROIs were drawn on structural magnetic resonance imaging (MRI) scans and projected onto the PET images in which regional CBF values and the water perfusable tissue fraction for the cortical gray matter tissue (hence the volume of gray matter) were estimated. After the PET study, the animals were killed and stereologic analysis was performed to assess the gray matter mass in the corresponding ROIs. Reproducibility of the estimated parameters and sensitivity to various error sources were also evaluated. All models tested in the current study yielded PVE-corrected regional CBF values (approximately 0.8 mL x min(-1) x g(-1) for models with a term for gray matter tissue and 0.5 mL x min(-1) x g(-1) for models with a term for a mixture of gray matter and white matter tissues). These values were greater than those obtained from ROIs tracing the gray matter cortex using conventional H2(15)O autoradiography (approximately 0.40 mL x min(-1) x g(-1)). Among the four models, configurations that included two parallel tissue compartments demonstrated better results with regards to the agreement of tissue time-activity curve and the Akaike's Information Criteria. Error sensitivity analysis suggested the model that fits three parameters of the gray matter CBF, the gray matter fraction, and the white matter fraction with fixed white matter CBF as the most reliable and suitable for estimating the gray matter CBF. Reproducibility with this model was 11% for estimating the gray matter CBF. The volume of gray matter tissue can also be estimated using this model and was significantly correlated with the results from the stereologic analysis. However, values were significantly smaller compared with those measured by stereologic analysis by 40%, which can not be explained by the methodologic errors. In conclusion, the partial volume correction was essential in quantitation of regional CBF. The method presented in this article provided the PVE-corrected regional CBF in the cortical gray matter tissue. This study also suggests that further studies are required before using MRI derived anatomic information for PVE correction in PET.

Animals↗

PubMed2000

Quantitation of regional cerebral blood flow corrected for partial volume effect using O-15 water and PET: II. Normal values and gray matter blood flow response to visual activation.

One of the most limiting factors for the accurate quantification of physiologic parameters with positron emission tomography (PET) is the partial volume effect (PVE). To assess the magnitude of this contribution to the measurement of regional cerebral blood flow (rCBF), the authors have formulated four kinetic models each including a parameter defining the perfusable tissue fraction (PTF). The four kinetic models used were 2 one-tissue compartment models with (Model A) and without (Model B) a vascular term and 2 two-tissue compartment models with fixed (Model C) or variable (Model D) white matter flow. Furthermore, rCBF based on the autoradiographic method was measured. The goals of the study were to determine the following in normal humans: (1) the optimal model, (2) the optimal length of fit, (3) the model parameters and their reproducibility, and (4) the effects of data acquisition (2D or 3D). Furthermore, the authors wanted to measure the activation response in the occipital gray matter compartment, and in doing so test the stability of the PTF, during perturbations of rCBF induced by visual stimulation. Eight dynamic PET scans were acquired per subject (n = 8), each for a duration of 6 minutes after IV bolus injection of H2(15)O. Four of these scans were performed using 2D and four using 3D acquisition. Visual stimulation was presented in four scans, and four scans were during rest. Model C was found optimal based on Akaike's Information Criteria (AIC) and had the smallest coefficient of variance after a 6-minute length of fit. Using this model the average PVE corrected rCBF during rest in gray matter was 1.07 mL x min(-1) x g(-1) (0.11 SD), with an average coefficient of variance of 6%. Acquisition mode did not affect the estimated parameters, with the exception of a significant increase in the white matter rCBF using the autoradiographic method (2D: 0.17 mL x min(-1) x g(-1) (0.02 SD); 3D: 0.21 mL x min(-1) x g(-1) (0.02 SD)). At a 6-minute fit the average gray matter CBF using Models C and D were increased by 100% to 150% compared with Models A and B and the autoradiographic method. There were no significant changes in the perfusable tissue fraction by the activation induced rCBF increases. The largest activation response was found using Model C (median = 39.1%). The current study clearly demonstrates the importance of PVE correction in the quantitation of rCBF in normal humans. The potential use of this method is to cost-effectively deliver PVE corrected measures of rCBF and tissue volumes without reference to imaging modalities other than PET.

Adult↗

PubMed1999

Generalizable patterns in neuroimaging: how many principal components?

Generalization can be defined quantitatively and can be used to assess the performance of principal component analysis (PCA). The generalizability of PCA depends on the number of principal components retained in the analysis. We provide analytic and test set estimates of generalization. We show how the generalization error can be used to select the number of principal components in two analyses of functional magnetic resonance imaging activation sets.

Algorithms↗

PubMed1998

Brain activation during word identification and word recognition.

Previous memory research has suggested that the effects of prior study observed in priming tasks are functionally, and neurobiologically, distinct phenomena from the kind of memory expressed in conventional (explicit) memory tests. Evidence for this position comes from observed dissociations between memory scores obtained with the two kinds of tasks. However, there is continuing controversy about the meaning of these dissociations. In recent studies, Ostergaard (1998a, Memory Cognit, 26:40-60; 1998b, J. Int. Neuropsychol. Soc., in press) showed that simply degrading visual word stimuli can dramatically alter the degree to which word priming shows a dissociation from word recognition; i.e., effects of a number of factors on priming paralleled their effects on recognition memory tests when the words were degraded at test. In the present study, cerebral blood flow changes were measured while subjects performed the word identification (reading) and recognition memory tasks used previously by Ostergaard. The results are the direct comparisons of the two tasks and the effects of stimulus degradation on blood flow patterns during the tasks. Clear differences between word identification and word recognition were observed: the latter task evoked considerably more prefrontal activity and stronger cerebellar activation. Stimulus degradation was associated with focal increases in bilateral fusiform regions within the occipital lobe. No task, degradation, or item repetition effects were demonstrated in mesial temporal regions, no repetition effects were observed in any region, and there was no evidence for different effects of stimulus degradation in the priming and recognition memory conditions. Power limitations may have contributed to the null effects.

Adult↗

PubMed1998

Parieto-occipital cortex activation during self-generated eye movements in the dark.

A number of extrastriate visual areas in the parieto-occipital cortex are known from single-cell recordings of the macaque monkey to be involved in the coding of eye-position signals in the brain. These are important for the accurate location of visual objects in extrapersonal space. It can be predicted that these areas will show increased activation during the performance of eye movements at high frequency. In the present study PET and measurements of the regional distribution of cerebral blood flow (rCBF) were used as indirect measures of neural activity. Two independent groups of normal volunteers performed large-amplitude self-generated eye movements in complete darkness, thus removing the confounding effects of visual stimulation on parieto-occipital activation. The first group (group A; n = 5) served as a hypothesis-generating group and the second group (group B; n = 4) served as a hypothesis-testing group. The data were analysed using statistical parametric mapping at a significance level corrected for multiple comparisons (group A, Z > 4.08; group B, Z > 4.04). Significant rCBF increases were found for both groups in the frontal eye fields, supplementary eye fields, cerebellar vermis and putamina/thalami. Additionally, activation was found in the cunei in the posterior bank of the parieto-occipital sulcus. Also, the extraocular muscles were activated and, as a consequence of the partial volume effect, projected to the orbitofrontal cortices. At a less conservative threshold, activation was found close to the intraparietal sulci on the left side (Z = 3.91, P = 0.09) and right side (Z = 3.33, P = 0.42). The locations of these areas were confirmed in group B with reference to high-resolution structural MRI scans. The activation of the parieto-occipital cortex without overt visual stimuli is interpreted as the result of neural activity related to the reception of efferent copies of motor commands and/or the activation of neurons coding for eye position relative to the orbits. These are important constituents for the location and remapping of visual stimuli in space.

Adult↗

PubMed1998

Metabolic and hemodynamic evaluation of brain metastases from small cell lung cancer with positron emission tomography.

Brain metastases from small cell lung cancer respond to chemotherapy, but response duration is short and the intracerebral concentration of chemotherapy may be too low because of the characteristics of the blood-brain barrier. Positron emission tomography has been applied in a variety of tumors for studies of metabolic and hemodynamic features. This study was performed to determine regional cerebral metabolic rate of glucose (rCMRglu), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) in brain metastases from small cell lung cancer and the surrounding brain. Tumor rCMRglu, rCBF, and rCBV exerted a broad variability, but were higher than the corresponding values in white matter and higher than or similar to those of gray matter. Tumor rCMRglu and rCBF were highly correlated (P < 0.01, r = 0.79). No correlation between survival and metabolic or hemodynamic parameters could be demonstrated. After radiotherapy, mean tumor rCMRglu decreased from 0.40 to 0.31 micromol/g/min (not significant), and rCBF and rCBV remained unchanged. However, cortical rCBF demonstrated a trend of increased values after radiotherapy from 0.37 to 0.49 ml/g/min (P = 0.13). No change in rCMRglu was observed in gray or white matter after radiotherapy. Global CBF seems to be reversibly depressed by the metastases, but local hemodynamic changes in the tumor could not be detected with positron emission tomography in this study. An association between high tumor rCMRglu and rCBF as an indicator of hypoxia was not observed. Other methods for noninvasive in vivo analysis of tumor hemodynamics are needed, especially for discrimination between tumor necrosis and hypoxia.

Adolescent↗

PubMed1997

The activation pattern in normal humans during suppression, imagination and performance of saccadic eye movements.

The distribution of activated cerebral regions was examined in nine normal subjects during four different eye movement-related conditions: (1) fixation-fixation on a central light emitting diode; (2) saccadic suppression-fixation on a diode in the presence of flashing lateral targets; (3) reflexive/volitional saccades-performance of overt eye movements to two laterally lit targets and back to the centre; and (4) imagined saccades-imagining, but not performing, the same eye movements. The regional neural activity was measured indirectly using repetitive bolus injections of oxygen-15-labelled water and positron emission tomography (PET) to yield time-integrated images of the normalized count distribution. These were aligned and anatomically normalized to a standard stereotactic space and the averages of each condition were analysed categorically using statistical parametric mapping. Compared to central fixation, reflexive/volitional saccades significantly activated regions in the classically known cortical oculomotor regions. The most notable activation during the saccade suppression task, compared to central fixation alone, was a bilateral activation of the parietal cortex with a right-sided preponderance, activation of the supplementary eye field/caudal cingulate regions, and activation of frontal regions close to the frontal eye fields. Imagined performance of eye movements without overt eye movements activated the supplementary eye field and frontal eye fields identically to regions involved in overt eye movements, thus demonstrating that over eye movements are not a prerequisite of the activation of these regions in normal humans.

Adult↗

PubMed1996

Rate dependence of regional cerebral activation during performance of a repetitive motor task: a PET study.

Using repeated positron emission tomography (PET) measures of regional cerebral counts, we investigated the regional cortical activations induced in eight normal subjects performing eight different frequencies of fingertapping (0.5-4 Hz) with the right index finger. The task was auditorially cued and the performance recorded during the scanning procedure. Performance evaluation showed increased error rates, during fingertapping, of high and low frequencies, and the best tapping performance was measured in the midrange of frequencies. Significantly activated areas (p < 0.05) of normalized cerebral counts were located in the left sensorimotor cortex (MISI), right motor cortex, left thalamus, right insula, supplementary motor area (SMA), and bilaterally in the primary auditory cortex and the cerebellum. Statistical evaluation showed a significant (p < 0.01) and positive dependence of cerebral activation upon movement rate in the contralateral MISI. There was no significant rate dependence of cerebral activation in other activated motor areas. The SMA and the right cerebellar hemisphere showed a more uniform activation throughout the tapping frequency range. Furthermore, we found a stimulus rate dependence of cerebral activation in the primary auditory cortex. We believe that the present data provide useful information for the preparation and interpretation of future motor activation studies of normal human subjects and may serve as reference points for studies of pathological conditions.

Adult↗

PubMed1993

A quantitative study of pruning by optimal brain damage.

The optimal brain damage (OBD) scheme of Le Cun, Denker and Solla for pruning of feedforward networks has been implemented and applied to the contiguity classification problem. It is shown that OBD improves the learning curve (the test error as a function of the number of examples). By inspecting the architectures obtained through pruning, it is found that the networks with less parameters have the smallest test error in agreement with "Ockhams Razor". Based on this, we propose a heuristic which selects the smallest successful architecture among a group of pruned networks and we show that it leads to very efficient optimization of the architecture. The validity of the approximations involved in OBD are discussed and it is found that they are surprisingly accurate for the problem studied.

Animals↗

PubMed1989

An investigation of the effect of regional variation in the treatment of hypertension.

Over a period both a monetary and physical measure of antihypertensive drug consumption has increased in Denmark, but the consumption has varied considerably between counties in any given year. Concurrently, SMR for myocardial infarctions and cerebrovascular diseases due to hypertension has declined. The relation between intensity of treatment and outcome in terms of reduced loss of life time or healthy time is analyzed at an aggregate level within a health economic framework. The relation is analyzed by using a pooled time series cross section regression analysis. Two models, a covariance and an error component model are used. Within the range of observed drug consumption, loss of life years and loss of good health show a tendency towards negative regression on consumption of drugs when controlled for relevant variables such as occupational structure, degree of urbanization, and hardness of the drinking water.

Antihypertensive Agents↗