The cerebral blood flow, CBF, is an important clinical parameter in neuro-intensive care. The possibility to continuously monitor CBF, computed from referential ICP, rICP (calculated from measured intracranial pressure, ICP, and central venous pressure, CVP) and venous outflow resistance, Rv, could importantly improve patient care. For the CBF(1) method the pulsative part of CBF (with rICP increase due to vascular volume increase) gives the venous outflow resistance, Rv. The CBF max method finds Rv from the close correlation between rICP and Rv. For both CBF(1) and CBF max, rICP divided with Rv gives CBF. The parameters rICP, Rv and CBF were calculated from measurements of ICP increase, and of intracerebral venous volume increase in nine subjects, by the CBF(1) method. The result, together with the finding of a close correlation between rICP and Rv, which made CBF dependent on rICP only, gave confirmation of the theory for computation of CBF, with two methods for continuous monitoring of CBF from rICP, one (CBF(1)) using the systolic ICP increase to find Rv, and one (CBF max) using the relationship between Rv and rICP at rICP exceeding about 10 mmHg in this study.

One of the primary objectives in forensic psychiatry, distinguishing it from other psychiatric disciplines, is risk management. Assessments of the risk of criminal recidivism are performed on a routine basis, as a baseline for risk management for populations involved in the criminal justice system. However, the risk assessment tools available to clinical practice are limited in their ability to predict recidivism. Recently, the prospect of incorporating neuroimaging data to improve the prediction of criminal behavior has received increased attention. In this study we investigated the feasibility of including neuroimaging data in the prediction of recidivism by studying whether the inclusion of resting-state regional cerebral blood flow measurements leads to an incremental increase in predictive performance over traditional risk factors. A subsample (N = 44) from a cohort of forensic psychiatric patients who underwent single-photon emission computed tomography neuroimaging and clinical psychiatric assessment during their court-ordered forensic psychiatric investigation were included in a long-term (ten year average time at risk) follow-up. A Baseline model with eight empirically established risk factors, and an Extended model which also included resting-state regional cerebral blood flow measurements from eight brain regions were estimated using random forest classification and compared using several predictive performance metrics. Including neuroimaging data in the Extended model increased the area under the receiver operating characteristic curve (AUC) from .69 to .81, increased accuracy from .64 to .82 and increased the scaled Brier score from .08 to .25, supporting the feasibility of including neuroimaging data in the prediction of recidivism in forensic psychiatric patients. Although our results hint at potential benefits in the domain of risk assessment, several limitations and ethical challenges are discussed. Further studies with larger, carefully characterized clinical samples utilizing higher-resolution neuroimaging techniques are warranted.

OBJECTIVES:Constant infusion lumbar infusion test (LIT) is an important way to find which patients, of those with signs and symptoms corresponding to normal pressure hydrocephalus (NPH) who will improve from shunt operation. LIT is a stress test on the ability for cerebrospinal fluid re-absorbtion. The aim of this study is to show how the information from LIT can be improved by quantitative analysis and avoidance of methodological pitfalls. MATERIAL AND METHODS:The potential pitfalls, and the analysis method, are described in detail. The analysis was applied on pre-operative constant infusion LIT from 31 patients operated for NPH, with known outcome. The pre- and post-operative walking speed was used to grade pathology progression or improvement. RESULTS:The maximal, plateau, intra-spinal pressure at constant infusion LIT is an ambivalent indicator for NPH: while low maximal pressure indicates no cerebrospinal fluid (CSF) absorbtion pathology, too high pressure (≥47 mmHg) may mean no diagnosis, because of stenosis of the Sylvian aqueduct. When subjects with too high intra-spinal pressure were excluded, the new analysis gave a couple of diagnostic volume parameters, of which one appears to be an optimal LIT parameter for identifying NPH patients with 14% better accuracy than plateau pressure. CONCLUSION:By avoiding methodological pitfalls, and optimal analysis of the results from lumbar infusion test, the number of NPH patients who do not have a successful outcome after shunt operation may be further decreased.

Objective: The physiological background for intracranial pressure, ICP, increase at brain compression is presently unknown. Current knowledge of the relationship between ICP and volume of brain compression is based on animal experiments, which has led to the theory of elastic brain tissue compression, which like a loaded spring causes the ICP increase. However, tests of brain tissue composition, or compression, find no basis for elasticity, or compression. The aim of this article is to describe the physiological features controlling ICP since it is necessary for the understanding of intracranial physiology, but also since ICP is an important parameter in neurointensive care medicine. Methods: This evaluation is based on the physiological consequences of the closed intracranial compartment, the thin-walled, compressible venous bed, the auto-regulation of cerebral blood flow, CBF, to blood pressure changes, and the coupling between ICP and the intra-capillary blood pressure through the thin, flexible capillary wall. These features influence the intracranial venous blood volume, the venous vascular resistance, and the CBF. Together these features are shown to revile the ICP dependence on the volume of brain volume compression. Results: The evaluation leads to a formula that describes the relationship between ICP and changes in the brain volume. The formula predicts an exponential ICP increase at brain compression like in animal experiments but, contrary to the elastic tissue theory, a gradually higher exponential for larger compression. Conclusion: The found relationship between ICP and changes in brain volume may prove to be a useful tool in neuro-intensive care patients for following changes in intracranial volumes by the aid of continuous ICP measurements. Since brain-compressing volumes includes the arterial pulse volume, the ICP formula may also enable CBF calculation from ICP measurements. The physiological relationships leading to the description of the relationship between ICP and brain volume change may by themselves help in understanding other intracranial phenomena, like ICP plateau-waves.

Background: The preclinical patterns of biological markers for Alzheimer’s disease (AD) in vivo needs further exploration. The aim of this study was therefore to investigate CSF biomarkers, regional cerebral blood flow (rCBF) and cognitive performance in cognitively healthy older individuals. Method: Within a two weeks period, 32 cognitively healthy older individuals underwent CSF analysis, rCBF measurement, and cognitive testing. The CSF was analysed for β-amyloid1-42 (Aβ42), total tau protein (T-tau), and hyperphosphorylated tau protein (P-tau). The rCBF results were analysed with SPM (statistical parametric mapping) to investigate rCBF covariance with the other measurements. Results: High CSF P-tau and T-tau levels correlated with decreased rCBF in the right superior posterior medial frontal lobe whereas high CSF P-tau levels also correlated with increased rCBF in the left fronto-temporal border zone area. No significant covariance was seen between rCBF with CSF Aβ42. Neither CSF P-tau and T-tau levels nor rCBF in the current right frontal and left posterior locations were associated with cognitive performance. Conclusions: Our findings suggest a possible correlation between tau pathology and blood flow abnormalities in individuals without any overt cognitive symptoms. An association with AD development is possible but other explanatory mechanisms cannot be excluded.

BACKGROUND:Cerebral blood flow (CBF) measurements are helpful in managing patients with traumatic brain injury (TBI), and testing the cerebrovascular reactivity to CO(2) provides information about injury severity and outcome. The complexity and potential hazard of performing CBF measurements limits routine clinical use. An alternative approach is to measure the CBF velocity using bedside, non-invasive, and transcranial Doppler (TCD) sonography. This study was performed to investigate if TCD is a useful alternative to CBF in patients with severe TBI.METHOD:CBF and TCD flow velocity measurements and cerebrovascular reactivity to hypocapnia were simultaneously evaluated in 27 patients with acute TBI. Measurements were performed preoperatively during controlled normocapnia and hypocapnia in patients scheduled for hematoma evacuation under general anesthesia.MAIN FINDING AND CONCLUSION:Although the lack of statistical correlation between the calculated reactivity indices, there was a significant decrease in TCD-mean flow velocity and a decrease in CBF with hypocapnia. CBF and TCD do not seem to be directly interchangeable in determining CO(2)-reactivity in TBI, despite both methods demonstrating deviation in the same direction during hypocapnia. TCD and CBF measurements both provide useful information on cerebrovascular events which, although not interchangeable, may complement each other in clinical scenarios.

Background: The preclinical patterns of biological markers for Alzheimer’s disease (AD) in vivo need further exploration. The aim of this study was therefore to investigate CSF biomarkers, regional cerebral blood flow (rCBF) and cognitive performance in cognitively healthy older individuals. Method: Within a 2-week period, 32 cognitively healthy older individuals underwent CSF analysis, rCBF measurement and cognitive testing. The CSF was analysed for β-amyloid1–42 (Aβ42), total tau protein (T-tau) and hyperphosphorylated tau protein (P-tau). The rCBF results were analysed with statistical parametric mapping to investigate rCBF covariance with the other measurements. Results: High CSF P-tau and T-tau levels correlated with decreased rCBF in the right superior posterior medial frontal lobe whereas high CSF P-tau levels also correlated with increased rCBF in the left fronto-temporal border zone area. No significant covariance was seen between rCBF and CSF Aβ42. Neither CSF P-tau and T-tau levels nor rCBF in the current right frontal and left posterior locations were associated with cognitive performance. Conclusions: Our findings suggest a possible correlation between tau pathology and blood flow abnormalities in individuals without any overt cognitive symptoms. An association with AD development is possible but other explanatory mechanisms cannot be excluded.

Most nuclear medicine clinicians use only visual assessment when interpreting regional cerebral blood flow (rCBF) from single-photon emission computed tomography (SPECT) images in clinical practice. The aims of this study were to develop a new, easy to use, automated method for quantification of rCBF-SPECT and to create normal values by using the method on a normal population. We developed a 3-dimensional method based on a brain-shaped model and the active-shape algorithm. The method defines the surface shape of the brain and then projects the maximum counts 0-1.5 cm deep for designated surface points. These surface projection values are divided into cortical regions representing the different lobes and presented relative to the whole cortex, cerebellum or cerebellar maximum. (99m) Tc-hexa methyl propylene amine oxime (HMPAO) SPECT was performed on 30 healthy volunteers with a mean age of 74 years (range 64-98). The ability of the active-shape algorithm to define the shape of the brain was satisfactory when visually scrutinized. The results of the quantification show rCBF values in the frontal, temporal and parietal lobes of 87-88% using cerebellum as the reference. There were no significant differences in normal rCBF values between male and female subjects and only a weak relation between rCBF and age. In conclusion, our new automated method was able to quantify rCBF-SPECT images and create normal values in ranges as expected. Further studies are needed to assess the clinical value of this method and the normal values.

Magnetic resonance imaging was used to compare subcortical volumes of seven suicide attempters with those of six healthy controls. Suicide attempters had 10% smaller right caudate nucleus and 19% bilaterally smaller globus pallidus. In suicide attempters, volumes of the globus pallidus correlated negatively with previously reported measures of solidity (non-impulsive temperament) and serotonin transporter binding potential.

Cerebral perfusion parameters were measured using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) in eight healthy volunteers examined during normal breathing and spontaneous hyperventilation. DSC-MRI-based cerebral blood flow (CBF) decreased during hyperventilation in all volunteers (average decrease 29%), and the corresponding global CBF estimates were 73 plusmn 19 ml/(min 100 g) during normal breathing and 52 plusmn 7.9 ml/(min 100 g) during hyperventilation (mean plusmn SD, n = 8). Furthermore, the hypocapnic conditions induced by hyperventilation resulted in a prolongation of the mean transit time (MTT) by on average 13%. The observed CBF estimates appeared to be systematically overestimated, in accordance with previously published DSC-MRI results, but reduced to more reasonable levels when a previously retrieved calibration factor was applied.

Background: The serotonergic system, including the serotonin transporter (5-HTT), which is the target of many antidepressants, seems to be influenced by brain-derived neurotrophic factor (BDNF).Methods: Positron emission tomography (PET) was used to address, in 25 and 53 healthy volunteers, respectively, the possible association between six polymorphisms in the gene encoding BDNF and the availability of two proteins expressed by serotonergic neurons: the 5-HTT, measured with the radioligand [C-11]MADAM, and the serotonin-1A (5-HT1A) receptor, measured with [C-11]WAY-100635.Results: Several single nucleotide polymorphisms were associated with [C-11]MADAM binding potential (BP) in most brain regions, male carriers of the valine/valine genotype of the Val66Met polymorphism displaying higher availability. Effect sizes ranged from a 50% to a threefold increase. In contrast, there was no association for [C-11]WAY-100635 BP. The observation that BDNF polymorphisms were associated with 5-HTT availability could be partly replicated in an independent population comprising nine male suicide attempters and nine matched control subjects, in which transporter availability had been measured with single photon emission computed tomography with I-123-beta-CIT as ligand.Conclusions: Our results suggest that genetic variation in BDNF influences 5-HTT but not 5-HT1A receptor density in the human brain.

The efficacy of serotonin reuptake inhibitors in depression and anxiety disorders suggests the gene coding for the serotonin transporter (5-HTT), SLC6A4, as a candidate of importance for these conditions. Positive findings regarding associations between polymorphisms in SLC6A4 have been reported, indicating that these polymorphisms may influence anxiety-related personality traits, as well as the risk of developing depression and suicidality. Serotonin 5-HTT availability was assessed with single photon emission computed tomography (SPECT), using (123)I-beta-CIT as ligand, in a population of unmedicated male suicide attempters (n=9) and in matched controls (n=9). Two polymorphisms in SLC6A4 were assessed, including the 5-HTTLPR located in the promoter region and a variable number of tandem repeats (VNTR) polymorphism in intron 2 (STin2). In suicide attempters, but not in controls, low 5-HTT availability was associated with the S allele of 5-HTTLPR and with the 12 repeat allele of STin2. Data suggest that polymorphisms in SLC6A4 may influence the expression of the brain serotonin transporter in suicide attempters.

Methods. Regional CMRglu (rCMRglu) was measured three dimensionally with positron emission tomography (PET) after injection of 2-(F)fluoro-2-deoxy-D-glucose in 10 spontaneously breathing men (mean age 31 yr) inhaling either N2O 50% in O2 30% or O2 30% in N2. Results. Global CMRglu in young men was 27 (3) mmol 100 g 21 min [mean (SD)]. Inhalation of N2O 50% did not change global CMRglu [30 (5) mmol 100 g 21 min] significantly, but it changed the distribution of the metabolism in the brain (P,0.0001 analysis of variance). Compared with inhalation of O2 30% in N2, N2O 50% inhalation increased the metabolism in the basal ganglia [14 (17)%, P,0.05] and thalamus [22 (23) %, P,0.05]. There was a prolonged metabolic effect of N2O inhalation seen on a succeeding PET scan with oxygen-enriched air (P,0.0001) performed 1 h after the N2O administration. Conclusions. Inhalation of N2O 50% did not change global CMRglu, but the metabolism increased in central brain structures, an effect that was still present 1 h after discontinuation of N2O.

Background: Patients with elevated intracranial pressure risk compromising their cerebral blood flow, resulting in ischemia. Lowering of the raised intracranial pressure, is therefore, mandatory. Reduction of the cerebral blood volume (CBV) might be target. In finding ways to do so, one has to be able to measure CBV. Measurement of CBV is, however, difficult. Radio(Tc-99m-)labeled erythrocytes ((TcRBC)-Tc-99m) single photon emission computeraided tomography (SPECT) is one established method used for CBV measurement. Recently, dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI), has also been successfully used for this purpose. The aim of this study was to validate the use of DSC-MRI for the measurement of CBV by the investigation of the correlation between the regional distributions of Tc-99m-RBC SPECT and DSC-MRI measurement of CBV in humans. If possible, the aim was also to find a conversion constant that will enable the DCS-MRI to be interpreted as CBV (percent of brain volume).Methods: CBV of 8 volunteers were studied under normocapnic and hypocapnic conditions. CBV, was measured with both Tc-99m-RBC SPECT and DSC-MRI.Results: There were significant correlations between the regional distributions of CBV measured by Tc-99m-RBC SPECT and DSC-MRI (rest: F=4.53, P<0.05; hypocapnia: F=9.61, P < 0.005). The derived conversion factor between DSC-MRI voxel values and Tc-99m-RBC SPECT CBV (percent of brain volume) at rest was 0.0059 +/- 0.0013. Global CBV during normocapnia was 4.3% +/- 0.6% of brain volume as measured by SPECT of brain volume and 4.5% +/- 0.9% as measured by MRI. Decreasing the end-tidal PCO2 by 1.8 kPa by spontaneous hyperventilation reduced the global CBV significantly to 3.9% +/- 0.5% in the SPECT group and to 3.5% +/- 0.6% in the MRI group.Conclusions: The comparison of Tc-99m-RBC SPECT and DSC-MRI measurements in our study indicates that DSC-MRI can be a useful method to measure CBV as a percent of brain volume.

Serotonin and dopamine are two monoamines which are known to interact with each other. Their role for suicidal behaviour, aggression and mood are reviewed in this chapter. We found a substantial amount of evidence for the relevance of a serotonin and dopamine model of aggression, and for aggression as a major risk factor for suicide. Evidence was found that serotonin and dopamine also may be involved in depressed mood, and possibly the individual's ability to cope with imminent suicidality.