Attempts to improve absolute quantification of cerebral blood flow in dynamic susceptibility contrast magnetic resonance imaging: a simplified T1-weighted steady-state cerebral blood volume approach.

BACKGROUND: Attempts to retrieve absolute values of cerebral blood flow (CBF) by dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) have typically resulted in overestimations. PURPOSE: To improve DSC-MRI CBF estimates by calibrating the DSC-MRI-based cerebral blood volume (CBV) with a corresponding T1-weighted (T1W) steady-state (ss) CBV estimate. MATERIAL AND METHODS: 17 volunteers were investigated by DSC-MRI and 133Xe SPECT. Steady-state CBV calculation, assuming no water exchange, was accomplished using signal values from blood and tissue, before and after contrast agent, obtained by T1W spin-echo imaging. Using steady-state and DSC-MRI CBV estimates, a calibration factor K = CBV(ss)/CBV(DSC) was obtained for each individual. Average whole-brain CBF(DSC) was calculated, and the corrected MRI-based CBF estimate was given by CBF(ss) = K x CBF(DSC). RESULTS: Average whole-brain SPECT CBF was 40.1+/-6.9 ml/min x 100 g, while the corresponding uncorrected DSC-MRI-based value was 69.2+/-13.8 ml/min x 100 g. After correction with the calibration factor, a CBF(ss) of 42.7+/-14.0 ml/min x 100 g was obtained. The linear fit to CBF(ss)-versus-CBF(SPECT) data was close to proportionality (R = 0.52). CONCLUSION: Calibration by steady-state CBV reduced the population average CBF to a reasonable level, and a modest linear correlation with the reference 133Xe SPECT technique was observed. Possible explanations for the limited accuracy are, for example, large-vessel partial-volume effects, low post-contrast signal enhancement in T1W images, and water-exchange effects.

Electroencephalography and magnetic resonance imaging in neurological decompression sickness.

The purpose of this study was to evaluate the use of electroencephalography (EEG) and magnetic resonance imaging (MRI) in the clinical evaluation of acute decompression sickness (DCS) in the central nervous system (CNS). Twenty-one patients treated because of acute DCS in the CNS during 1999-2001 were included, 15 patients with clinical cerebral DCS and five with clinical spinal cord DCS. Seven patients had abnormalities in their EEG, five with cerebral DCS and two with spinal cord DCS. MRI showed high intensity lesions in the spinal cord in four patients with clinical spinal cord DCS and in one with clinical cerebral DCS. Cerebral lesions were not identified by MRI in any patient. In conclusion, EEG showed unspecific abnormalities in only one third of the cases. Conventional MRI with a 1.5 T scanner may be of help in the diagnosis of DCS in the spinal cord, but not in the brain. EEG and MRI have low sensitivity in the diagnosis of acute DCS in the CNS. Recompression treatment of DCS should still be guided by clinical neurological examination and assessment of symptoms.

Venous gas embolism in chamber attendants after hyperbaric exposure.

An initial occupational survey (OS) was initiated to investigate the prevalence of venous gas embolism (VGE) in chamber attendants assisting hyperbaric oxygen (HBO2) treatments. Nine female subjects were exposed for three consecutive days to the routine hospital procedure of compressed air exposure to 240 kPa for approximately 115 min with 12 min of terminal oxygen (O2) breathing. VGE was monitored with ultrasound Doppler in 15 min intervals for 2h after the first and third exposure. A follow-up experimental study was completed to investigate whether changed breathing gases and decompression would affect the high incidence of VGE observed in the OS. Ten female subjects were randomly exposed to the routine or revised profile (12 and 24 min of terminal O2 breathing respectively), and a Nitrox profile (breathing gas 40.5% O2 in Nitrogen during 90 min of the isobaric phase). VGE was monitored with transthoracic ultrasound scanner and Doppler. In the OS precordial VGE grade III (Doppler) was observed in five subjects, but median resting precordial VGE was Grade 0 both days and VGE score at all sites were equal Days 1 and 3. In the experimental study, median resting precordial VGE was Grade 0 (Doppler) and Grade 1 (Scanner). VGE Grade III (Doppler) was observed in all series, but VGE scores were not significantly different between the series. We conclude that chamber attendants assisting HBO2 treatment at 240 kPa for approximately 115 min are exposed to a significant decompression stress using the profiles tested in the present study.

Subjective experience of memory deficits related to clinical and neuroimaging findings.

The aim of this study was to evaluate cognitive impairment, psychiatric symptoms and cerebral blood flow (CBF) patterns in middle-aged (35-64 years) and younger old patients (65-74 years) with subjective experience of memory deficits. The study group was heterogeneous with patients fulfilling criteria for dementia, as well as patients with mild cognitive impairment (MCI) and with non-verified cognitive impairment (non-MCI). Seventy per cent of the non-MCI patients reported long-lasting experiences of psychosocial stress tentatively causing the memory problems. The MCI patients were subdivided into two groups: MCI type 1 included patients with isolated memory impairment, while MCI type 2 included patients with memory impairment together with slight verbal and/or visuospatial impairments. CBF measurements comparing the two MCI groups with the non-MCI group were performed. The MCI type 2 showed reduced CBF in the left anterior medial temporal lobe as well as in parts of the posterior cingulate gyrus. The CBF pattern in MCI type 2 concurs with the pathophysiological process of Alzheimer's disease. The results indicate that it is important to make a subdivision of MCI patients regarding the presence of isolated memory impairments or memory impairments together with other slight cognitive deficits.

Contributions of other brain pathologies in dementia with lewy bodies.

The clinical picture with its pathological correlate was analysed in 16 patients fulfilling consensus criteria for dementia with Lewy bodies (DLB). The cases were part of a larger cohort (n = 200) of patients within a prospective longitudinal study of dementing disorders. Six cases exhibited not only Lewy bodies (LBs) but also other brain pathologies such as Alzheimer changes, multiple infarcts or complete and incomplete white matter infarcts. Degeneration of the nucleus basalis of Meynert and substantia nigra was also seen. The 10 cases without LBs all had Alzheimer changes. In 7 cases, these changes were combined with mainly incomplete frontal white matter infarcts. However, the degeneration of brain stem nuclei was less pronounced in these cases. Symptoms such as fluctuations in cognition, falls and episodic confusion appeared in association with arterial hypotension, which developed during the course of dementia in almost all the 16 cases. The majority of the cases were treated with neuroleptics and other potentially hypotensive medication. This study shows that multiple and different pathological features may contribute to a clinical symptom constellation as in DLB. The case study approach reveals the complexity of the clinico-pathological relationships in dementia that might otherwise be lost in the analysis of larger group data.

Cardiovascular effects of verapamil and quinidine at normal and elevated ambient pressure.

Cardiovascular parameters were measured in rats before and after administration of verapamil and quinidine, a slow Ca2+ and fast Na+ channel blocker, respectively, at normal and elevated ambient pressure [5 bar (500 kPa)]. Left ventricular pressure (Pivt), maximal velocity of Plvt rise (+dP/dt) and fall (-dP/dt), and heart rate (HR), arterial systolic pressure (Pasys), and mean arterial pressure (MAP) were measured in all animals using catheters connected to pressure transducers. Cardiac output (Q), and myocardial blood flow (MBF) were detected by the microsphere technique. Total peripheral vascular resistance (TPVR), myocardial vascular resistance (MVR) and oxygen consumption of the heart (VO2) was calculated. In Groups 1a (control group; 1 bar) and 1b (test group; 1-5 bar), verapamil (1.5 mg x kg(-1)) caused a reduction in Plvt, +dP/dt, -dP/dt, Pasys, MAP, VO2, TPVR, and MVR in both groups at 1 bar (100 kPa), and these parameters remained depressed for at least 50 min in Group 1a. However, MBF increased after verapamil injection. After compression to 5 bar (500 kPa), Plvt, dP/dt, Pasys, VO2, and MBF were markedly elevated (Group 1b). No change in HR, SV, or Q was found in either of the groups. In Groups 2a (control group; 1 bar) and 2b (test group; 1-5 bar), quinidine (5 mg x kg(-1)), infused over a period of 10 min, reduced Plvt, +dP/dt, -dP/dt, MAP, Pasys, VO2, Q, stroke volume (SV), TPVR and MBF at 1 bar (100 kPa). These parameters remained depressed for almost the whole experimental period in Group 2a, while Plvt, +/-dP/dt, Pasys, MAP and VO2 were enhanced during exposure to 5 bar (500 kPa) in Group 2b. The HR was unchanged by quinidine in Group 2a, but was increased at elevated ambient pressure in Group 2b, whereas the MBF was unchanged in both groups. The present results show that verapamil and quinidine have a depressant effect on cardiac function, arterial pressure and VO2 at normal atmospheric pressure, whereas MBF was enhanced only in the verapamil group. During exposure to elevated ambient pressure, cardiac function, arterial pressure and VO2 increased despite adequate inhibition of slow Ca2+ and fast Na+ channels.

Ethanol reduces rCFB activation of left dorsolateral prefrontal cortex during a verbal fluency task.

In a previous study in normal subjects (Wendt et al., 1994), using a reversing checkerboard as activation stimulus, we found that the coupling between local neuronal activity and regional cerebral blood flow was preserved following ethanol, and that a right-sided occipital activation response seen during sobriety became symmetrical during inebriation. In the present study we investigated if ethanol has a detrimental effect also on the activation of the left dorsolateral prefrontal cortex found in normals during verbal fluency. Measurements of regional cerebral blood flow in 20 healthy, young, male, right-handed volunteers during rest and verbal fluency were made during sobriety and inebriation (0.06% blood alcohol concentration) with a 1-week interval. We found a decrease in word production during inebriation. The normal activation within the frontotemporal part of the left dorsolateral prefrontal cortext was preserved during inebriation. The activation of this region seems thus to be robust to the effects of ethanol. During inebriation no activation response to the word fluency test was found in the anterior prefrontal part of the dorsolateral prefrontal cortex. This region is important for working, temporal, and short-term memory functions, processes that are affected by ethanol. Hemispheric functioning and specialization seem to be adversely affected by ethanol, regardless of which hemisphere is most involved while sober.

Thermal insulation properties of argon used as a dry suit inflation gas.

Uncontrolled observations from the "technical" diving community claim superior thermal comfort when replacing air with argon as dry suit inflation gas during diving. The objective of the present experiment was to evaluate the effectiveness of argon compared to air during cold water diving. Body weight, urinary output, and rectal and skin temperatures were measured in six naval divers during two dives to approximately 10 m for 60 min. Level of thermal comfort was reported. Dry suit gas was either argon or air, divers and scientists were blinded for gas identity. Urinary output was approximately 200 ml less (P < 0.05) during the air than the argon dives. Rectal and all skin temperatures decreased significantly in both groups during the dive but no difference was measured between argon and air dives. Thermal comfort was not different between the groups. Replacing air with argon neither improves subjective impression of thermal comfort nor attenuates core or skin cooling during cold water diving to 10 meters of sea water for 60 min.

On the neurobiology of creativity. Differences in frontal activity between high and low creative subjects.

The aim was to investigate the relationship between creativity and hemispheric asymmetry, as measured by regional cerebral blood flow (rCBF). Two groups, each consisting of 12 healthy male subjects, who got either very high or low scores on a creativity test, were pre-selected for the rCBF investigation. rCBF was measured during rest and three verbal tasks: automatic speech (Auto), word fluency (FAS) and uses of objects (Brick). State and trait anxiety inventories were answered after the rCBF measurements. Intelligence tests were also administered. It was predicted that highly creative subjects would show a bilateral frontal activation on the divergent thinking task (Brick), while low creative subjects were expected to have a unilateral increase. Calculations were made of differences in blood flow levels between the FAS and the Brick measurements in the anterior prefrontal, frontotemporal and superior frontal regions. In accordance with our prediction, repeated measure-ANOVAs showed that the creativity groups differed significantly in all three regions. The highly creative group had increases, or unchanged activity, while the low creative group had mainly decreases. The highly creative group had higher trait anxiety than the low creative group. On the intelligence tests the low creative group was superior both on logical-inductive ability and on perceptual speed, while the groups were equal on verbal and spatial tests. The results are discussed in terms of complementary functions of the hemispheres.

The cognitive neuroscience of signed language.

The present article is an assessment of the current state of knowledge in the field of cognitive neuroscience of signed language. Reviewed lesion data show that the left hemisphere is dominant for perception and production of signed language in aphasics, in a fashion similar to spoken language aphasia. Several neuropsychological dissociations support this claim: Non-linguistic visuospatial functions can be dissociated from spatial functions and general motor deficits can be dissociated from execution of signs. Reviewed imaging data corroborate the lesion data in that the importance of the left hemisphere is re-confirmed. The data also establish the role of the right hemisphere in signed language processing. Alternative hypotheses regarding what aspects of signed language processing are handled by the right hemisphere are currently tested. The second section of the paper starts by addressing the role that early acquisition of signed and spoken language play for the neurofunctional activation patterns in the brain. Compensatory cognitive and communicative enhancements have also been documented as a function of early sign language use, suggesting an interesting interaction between language and cognition. Recent behavioural data on sign processing in working memory--a cognitive system important for language perception and production suggest e.g. phonological loop effects analogous to those obtained for speech processing. Neuroimaging studies will have to address this potential communality.

Synapse density related to cerebral blood flow and symptomatology in frontal lobe degeneration and Alzheimer's disease.

In order to evaluate the functional significance of synaptic pathology, synaptic density was quantitated and related to clinical symptomatology and regional cerebral blood flow (rCBF) in 8 patients with frontal lobe degeneration of non-Alzheimer type (FLD) and 19 patients with Alzheimer's disease (AD). Synaptic density was measured in all layers of prefrontal and parietal cortex. The clinical picture of FLD was dominated by a frontal lobe syndrome with changes in personality and behavior, while AD was dominated by temporoparietal symptoms. This parallels the finding of frontal rCBF reductions in FLD patients and temporoparietal reductions in AD patients. Synaptic density was significantly decreased in both FLD and AD, with a regional severity which closely correlated with that of the degeneration, symptomatology and rCBF deficit. The results suggest that synaptic pathology is a likely cause of clinical symptoms and regional metabolic decrement in dementia.

A speechreading expert: the case of MM.

The present case study of MM, who acquired both sign language and spoken language in her early preschool years-and then reached the normal milestones of development in each language--revealed that her speechreading expertise is associated with cognitive functions such as high working memory capacity and phonological skills. Her cognitive profile is in accord with previous case studies of extremely good speechreading skill. MM's enhanced right prefrontal/frontal cerebral blood flow activation during speechreading seems to be indicative of efficient visual scanning, but it is also possibly due to her strategy for phonological decoding of visual speech.

Lateralized frontal blood flow increases during fluency tasks: influence of cognitive strategy.

Difficulties with verbal fluency tasks (VFIT) have been shown mainly to be associated with left frontal lobe pathology in lesion studies. The design fluency test (DFT) is a non-verbal analogue of word fluency tasks and has, in patients with right frontal lobe pathology, been coupled to an inability to perform well. Regional cerebral blood flow measurements (rCBF) were made in normals to elucidate the involvement of frontal and frontotemporal brain regions during the performance of VFT and DFT. In addition, the subjects' reports were used for obtaining information about the cognitive strategy used when solving the tasks. The results confirm previous CBF findings showing a mainly left-sided frontal activation during the VFT. During the DFT significant flow augmentations were seen in both frontal lobes compared to baseline. Furthermore, the use of different strategies was reflected in different patterns of brain activation. Our results support the proposal that the left frontal cortical area is engaged in the generation of internally driven responses. Furthermore, we argue that the cortical areas engaged during the execution of these tasks may reflect differences in cognitive strategy.

Diver's hand: a skin disorder common in occupational saturation diving.

Saturation divers regularly inspect North Sea installations, working at depth for periods of 12-16 days. Diver's hand is a particular problem in saturation diving, and there is no effective protection or treatment available. This paper presents the occurrence of diver's hand and describes the disease in clinical and epidemiological terms. Three studies of diver's hand have been carried out, in 1990, 1994, and 1995. Most long term saturation divers have had diver's hand at some time in their professional career. Diver's hand seems able to occur without any previous skin symptoms, and divers without diver's hand can have several other skin symptoms during a saturation period. It is likely that diver's hand is a specific phenomenon associated with saturation diving.

Alcohol activates the cerebral reward system in man.

OBJECTIVE: We investigated the effect of 0.07% alcohol on regional brain activity at rest and during cognitive performance in order to elucidate the anatomical substrate for the effects of alcohol in man as well as to clarify the interaction between changes in cerebral activity induced by cognitive performance and alcohol inebriation. METHOD: Regional cerebral blood flow (3D-PET, 15O Butanol) was measured in 13 male, nonalcoholic volunteers. Each subject was scanned 12 times, three scans in each of the following four situations: sober/rest, sober/test and inebriated/rest, inebriated/test. We used statistical parametric mapping and a computerized brain atlas for localization. RESULTS: Alcohol induced a sense of inebriation and elation as well as a relative increase of the cerebral blood flow in medial parts of the temporal lobes, in the anterobasal parts of the anterior cingulate cortex including the septal region. In addition, there was an increase of blood flow in midline parts of the lower brain stem. Relative decreases of flow were observed in the cerebellum and in the occipital cortex bilaterally. In the sober state, a computerized perceptual maze test and a (silent) serial seven test induced two distinct neocortical activation patterns that were specific to the tasks. Alcohol did not change these patterns and the test performance was also uninfluenced. CONCLUSIONS: A moderate dose of alcohol selectively activates target structures that pertain to the so-called cerebral reward system and the ascending reticular activating system. Alcohol (approximately 0.07%) appears to have only minor effects in the neocortical systems that are involved in on-line cognitive activity. This apparent independence between the subcortical alcohol target and the neocortical cognitive mechanisms is a new finding that appears to be of importance for an understanding of the effect of moderate doses of alcohol on the brain.

Brain function in spider phobia.

Measurements of regional cerebral blood flow (rCBF) were performed in 16 women suffering from spider phobia. The non-invasive 133Xe inhalation method, giving information about the blood flow of superficial areas, was used. The subjects were studied under three conditions: during resting, when exposed to a videotape showing nature scenery, and finally when watching a video with living spiders. During the rCBF measurements the subjects' behaviour was registered systematically and respiration, blood pressure, Pco2, and heart rate were monitored. Eight subjects who showed and reported severe panic during the spider exposure had marked rCBF decreases in frontal areas, especially in the right hemisphere. The remaining eight subjects displayed a more efficient control of their emotions and became frightened, but not panic-stricken, during the spider exposure. These showed a consistent rCBF increase in the right frontal area compared to neutral stimulation. Thus, results revealed significant functional changes in the frontal cortex in subjects with spider phobia during phobogenic exposure. It seems likely that these frontal changes are related to the experience and control of phobic anxiety.

Regional cerebral blood flow during signed and heard episodic and semantic memory tasks.

Ten deaf participants and 10 normal hearing participants performed 2 memory tasks during which their regional cerebral blood flow was measured with a high-resolution system. The deaf participants solved an episodic memory (i.e., recognition of words) and a semantic memory (i.e., classification of items into categories) task presented by means of sign language; the same material was presented to the hearing participants who heard the stimulus lists. The specific hypothesis that signed episodic recognition tasks would activate posterior, right-hemisphere cortical areas was supported. Expectedly, the remaining 3 memory activations were mainly located in the left hemisphere. Data from recent positron emission tomography studies suggest that one challenge for future research is to assess the relative localization for encoding and retrieval of signed episodes.

Regional cerebral blood flow measurements in the clinical evaluation of demented patients.

The clinical usefulness of two-dimensional measurements of regional cerebral blood flow (rCBF) for diagnosis of dementia is discussed on the basis of data from 150 patients with autopsy-based diagnosis. The specificity of Alzheimer's disease is found to be very good but the sensitivity only in the order of 75-80%, the majority of the mislabelled cases having selective incomplete white matter infarcts in addition to their Alzheimer pathology. Frontal lobe dementia is recognized by rCBF with high sensitivity but fairly low specificity due to the fact that frontal flow decreases are shared with several other disorders. Regarding cerebrovascular dementia the sensitivity is rather good (95%) while specificity is somewhat lower (70-75%). It is argued that rCBF should be interpreted diagnostically only when clear-cut findings are made preferably in a series of measurements. The noninvasiveness, repeatability, low radiation dose and low cost makes the present method an excellent tool for research as well as for clinical routine use.

The Swedish Centenarian Study: a multidisciplinary study of five consecutive cohorts at the age of 100.

UNLABELLED: Centenarians born 1887-91, who lived in southern Sweden were asked to participate in this multidisciplinary study (N = 164). Of the survivors (N = 143), 70 percent agreed (N = 100). The purpose was to describe the population from physical, social, and psychological points of view; to characterize centenarians with various health conditions and diverse degrees of autonomy and life satisfaction; and to identify factors at 100 years that predict future survival. RESULTS: Eighty-two percent were women, 25 percent lived in their own home, 37 percent in old age homes, and 38 percent in nursing homes. Socioeconomic status showed a similar distribution compared to nationally representative data. Fifty-two percent managed activities of daily living with or without minor assistance. The incidence of severe diseases was low. In 39 percent a disorder of the circulatory system was found. Thirty-nine percent (women) and 11 percent (men) had had at least one hip fracture. Twenty percent had good hearing and good vision. Twenty-seven percent were demented according to DSM III-R criteria. Means on cognitive tests (word-list, digit-span, learning, and memory) were lower compared to seventy to eighty year old groups. The variation in performance was extremely widespread. Personality profiles (MMPI) indicated that the centenarians were more responsible, capable, easygoing and less prone to anxiety than the population in general. Extensive neuropathological investigation revealed no major diseases or large lesions but mild through multiple changes. RESULTS suggest that centenarians are a special group genetically. A causal structure model emphasized body constitution, marital status, cognition and blood pressure as particularly important determinants for survival after 100 years.