Søren Holm

A 15O‐H2O PET study of meditation and the resting state of normal consciousness

The aim of the present study was to examine whether the neural structures subserving meditation can be reproducibly measured, and, if so, whether they are different from those supporting the resting state of normal consciousness. Cerebral blood flow distribution was investigated with the 15O‐H2O PET technique in nine young adults, who were highly experienced yoga teachers, during the relaxation meditation (Yoga Nidra), and during the resting state of normal consciousness. In addition, global CBF was measured in two of the subjects. Spectral EEG analysis was performed throughout the investigations. In meditation, differential activity was seen, with the noticeable exception of V1, in the posterior sensory and associative cortices known to participate in imagery tasks. In the resting state of normal consciousness (compared with meditation as a baseline), differential activity was found in dorso‐lateral and orbital frontal cortex, anterior cingulate gyri, left temporal gyri, left inferior parietal lobule, striatal and thalamic regions, pons and cerebellar vermis and hemispheres, structures thought to support an executive attentional network. The mean global flow remained unchanged for both subjects throughout the investigation (39 ± 5 and 38 ± 4 ml/100 g/min, uncorrected for partial volume effects). It is concluded that the H215O PET method may measure CBF distribution in the meditative state as well as during the resting state of normal consciousness, and that characteristic patterns of neural activity support each state. These findings enhance our understanding of the neural basis of different aspects of consciousness. Hum. Brain Mapping 7:98–105, 1999.

Persistent Resetting of the Cerebral Oxygen/Glucose Uptake Ratio by Brain Activation: Evidence Obtained with the Kety—Schmidt Technique:

Global cerebral blood flow (CBF), global cerebral metabolic rates for oxygen (CMRO2), and for glucose (CMRglc), and lactate efflux were measured during rest and during cerebral activation induced by the Wisconsin card sorting test. Measurements were performed in healthy volunteers using the Kety–Schmidt technique. Global CMRO2 was unchanged during cerebral activation, whereas global CBF and global CMRglc both increased by 12%, reducing the molar ratio of oxygen to glucose consumption from 6.0 during baseline conditions to 5.4 during activation. Data obtained in the period following cerebral activation showed that the activation-induced resetting of the relation between CMRglc and CMRO2 persisted virtually unaltered for ≥40 min after the mental activation task was terminated. The activation-induced increase in cerebral lactate efflux measured over the same time period accounted for only a small fraction of the activation-induced excess glucose uptake. These data confirm earlier reports that brain activation can induce resetting of the cerebral oxygen/glucose consumption ratio, and indicate that the resetting persists for a long period after cerebral activation has been terminated and physiologic stress indicators returned to baseline values. Activation-induced resetting of the cerebral oxygen/glucose uptake ratio is not necessarily accounted for by increased lactate production from nonoxidative glucose metabolism.

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 (M1S1), 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 M1S1. 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.

The relationship between cerebral blood flow and volume in humans

The purpose of this study was to establish the relationship between regional CBF and CBV at normal, resting cerebral metabolic rates. Eleven healthy volunteers were investigated with PET during baseline conditions, and during hyper- and hypocapnia. Values for rCBF and rCBV were obtained using 15O-labelled water and carbon monoxide, respectively. The mean value of rCBF using PET was 62 +/- 18 ml 100 g(-1) min(-1) during baseline conditions, with an average increase of 46% during hypercapnia, and a decrease of 29% during hypocapnia; baseline rCBV was 7.7 ml/100 g, with 27% increase during hypercapnia and no significant decrease during hypocapnia. A regionally uniform exponential relationship was confirmed between PaCO2 and rCBF as well as rCBV. It is shown that the theoretical implication of this is that the rCBV vs. rCBF relationship should be modelled by a power function; however, due to pronounced intersubject variability, the goodness of fit for linear and nonlinear models were not significantly different. The results of the study are applied to a numerical estimation of regional brain deoxy-haemoglobin content. Independently of the choice of model for the rCBV vs. rCBF relationship, a nonlinear deoxy-haemoglobin vs. rCBF relationship was predicted, and the implications for the BOLD response are discussed.

Attitudes towards clinical research amongst participants and nonparticipants

Abstract. Madsen SM, Mirza MR, Holm S, Hilsted KL, Kampmann K, Riis P (Copenhagen University Hospital in Herlev, Herlev, Denmark; Odense University Hospital in Odense, Odense C, Denmark; University of Manchester, Manchester, UK; Copenhagen University Hospital in Herlev, Herlev, Denmark; and Odense University Hospital in Odense, Odense C, Denmark). Attitudes towards clinical research amongst participants and nonparticipants. J Intern Med 2002; 251: 156–168.

Not just autonomy--the principles of American biomedical ethics.

The Principles of Biomedical Ethics by Tom L Beauchamp and James F Childress which is now in its fourth edition has had a great influence on the development of bioethics through its exposition of a theory based on the four principles: respect for autonomy; non-maleficence; beneficence, and justice (1). The theory is developed as a common-morality theory, and the present paper attempts to show how this approach, starting from American common-morality, leads to an underdevelopment of beneficence and justice, and that the methods offered for specification and balancing of principles are inadequate.

Average Blood Flow and Oxygen Uptake in the Human Brain During Resting Wakefulness: a Critical Appraisal of the Kety-Schmidt Technique

The Kety–Schmidt technique can be regarded as the reference method for measurement of global average cerebral blood flow (average CBF) and global average cerebral metabolic rate of oxygen (average CMRO2). However, in the practical application of the method, diffusion equilibrium for inert gas tracer between the brain and its venous blood is not reached. As a consequence, normal values for CBF and CMRO2 of 54 ml 100 g−1 min−1 and 3.5 ml 100 g−1 min−1 obtained with the Kety–Schmidt technique are an overestimation of the true values. Using the Kety–Schmidt technique we have performed 57 measurements of CBF and CMRO2 during EEG-verified wakeful rest in young normal adults. In order to estimate the equilibrium values for CBF and CMRO2, a simple computer-based simulation model was employed to quantitate the systematic overestimation caused by incomplete tracer equilibrium. When correcting the measured data, we find that the true average values for CBF and CMRO2 in the healthy young adult are ∼46 ml 100 g−1 min−1 and ∼3.0 ml 100 g−1 min−1. Previous studies have suggested that some of the variation in CMRO2 values could be ascribed to differences in cerebral venous anatomy. However in the present study, no correlation between CMRO2 and cerebral venous anatomy as imaged by magnetic resonance angiography could be established. Our data show that the interindividual variation of CMRO2 is 11% (coefficient of variation).

Combined PET/MR imaging in neurology: MR-based attenuation correction implies a strong spatial bias when ignoring bone☆

AIM Combined PET/MR systems have now become available for clinical use. Given the lack of integrated standard transmission (TX) sources in these systems, attenuation and scatter correction (AC) must be performed using the available MR-images. Since bone tissue cannot easily be accounted for during MR-AC, PET quantification can be biased, in particular, in the vicinity of the skull. Here, we assess PET quantification in PET/MR imaging of patients using phantoms and patient data. MATERIALS AND METHODS Nineteen patients referred to our clinic for a PET/CT exam as part of the diagnostic evaluation of suspected dementia were included in our study. The patients were injected with 200MBq [(18)F]FDG and imaged with PET/CT and PET/MR in random sequence within 1h. Both, PET/CT and PET/MR were performed as single-bed acquisitions without contrast administration. PET/CT and PET/MR data were reconstructed following CT-based and MR-based AC, respectively. MR-AC was performed based on: (A) standard Dixon-Water-Fat segmentation (DWFS), (B) DWFS with co-registered and segmented CT bone values superimposed, and (C) with co-registered full CT-based attenuation image. All PET images were reconstructed using AW-OSEM, with neither resolution recovery nor time-of-flight option employed. PET/CT (D) or PET/MR (A-C) images were decay-corrected to the start time of the first examination. PET images following AC were evaluated visually and quantitatively using 10 homeomorphic regions of interest drawn on a transaxial T1w-MR image traversing the central basal ganglia. We report the relative difference (%) of the mean ROI values for (A)-(C) in reference to PET/CT (D). In a separate phantom experiment a 2L plastic bottle was layered with approximately 12mm of Gypsum plaster to mimic skull bone. The phantom was imaged on PET/CT only and standard MR-AC was performed by replacing hyperdense CT attenuation values corresponding to bone (plaster) with attenuation values of water. PET image reconstruction was performed with CT-AC (D) and CT-AC using the modified CT images corresponding to MR-AC using DWFS (A). RESULTS PET activity values in patients following MR-AC (A) showed a substantial radial dependency when compared to PET/CT. In all patients cortical PET activity was lower than the activity in the central region of the brain (10-15%). When adding bone attenuation values to standard MR-AC (B and C) the radial gradient of PET activity values was removed. Further evaluation of PET/MR activity following MR-AC (A) relative to MR-AC (C) using the full CT for attenuation correction showed an underestimation of 25% in the cortical regions and 5-10% in the central regions of the brain. Observations in patients were replicated by observations from the phantom study. CONCLUSION Our phantom and patient data demonstrate a spatially varying bias of the PET activity in PET/MR images of the brain when bone tissue is not accounted for during attenuation correction. This has immediate implications for PET/MR imaging of the brain. Therefore, refinements to existing MR-AC methods or alternative strategies need to be found prior to adopting PET/MR imaging of the brain in clinical routine and research.

Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of silent metastases from malignant melanoma

Abstract.Correct staging is crucial for the management and prognosis of patients with malignant melanoma. The aim of this prospective study was to compare staging by whole-body positron emission tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) with staging by conventional methods. Thirty-eight patients with malignant melanoma of clinical stage II (local recurrence, in-transit and regional lymph node metastases) or III (metastases to other sites than in stage II) were included in the study. The results of the PET scans were compared with those obtained by clinical examination, computed tomography, ultrasound, radiography, and liver function tests and histology or clinical follow-up. With 18F-FDG PET we found for all foci a sensitivity of 97% and a specificity of 56%, compared with 62% and 22%, respectively, when using routine methods. For intra-abdominal foci, the sensitivity and specificity were 100% for both 18F-FDG PET and routine methods. Corresponding figures for pulmonary/intrathoracic foci were 100% and 33%, respectively. Of the patients included in this study, 34% would not have been staged correctly by conventional methods alone. We conclude from this study that 18F-FDG PET is a sensitive method superior to conventional methods for detecting widespread metastases from malignant melanoma. Mutilating surgery of no benefit can thereby be avoided. 18F-FDG PET is useful as a supplement to clinical examination in melanoma staging.

Unchanged cerebral blood flow and oxidative metabolism after acclimatization to high altitude.

The authors investigated the effect of acclimatization to high altitude on cerebral blood flow and oxidative metabolism at rest and during exercise. Nine healthy, native sea-level residents were studied 3 weeks after arrival at Chacaltaya, Bolivia (5,260 m) and after reacclimatization to sea level. Global cerebral blood flow at rest and during exercise on a bicycle ergometer was measured by the Kety-Schmidt technique. Cerebral metabolic rates of oxygen, glucose, and lactate were calculated by the Fick principle. Cerebral function was assessed by a computer-based measurement of reaction time. At high altitude at rest, arterial carbon dioxide tension, oxygen saturation, and oxygen tension were significantly reduced, and arterial oxygen content was increased because of an increase in hemoglobin concentration. Global cerebral blood flow was similar in the four conditions. Cerebral oxygen delivery and cerebral metabolic rates of oxygen and glucose also remained unchanged, whereas cerebral metabolic rates of lactate increased slightly but nonsignificantly at high altitude during exercise compared with high altitude at rest. Reaction time was unchanged. The data indicate that cerebral blood flow and oxidative metabolism are unaltered after high-altitude acclimatization from sea level, despite marked changes in breathing and other organ functions.