Analysis of Intracranial Pressure Pulse-Pressure Relationship: Experimental Validation.

The slope of linear relationship between the amplitude of pulsations in intracranial pressure (ICP) versus mean ICP has recently been suggested as a useful guide for selecting patients for shunt surgery in normal pressure hydrocephalus (NPH). To better understand how the pathophysiology of cerebral circulation influences this parameter, we aimed to study the relationship between mean pressure and pulsation amplitude in a wide range of conditions affecting cerebrovascular tone and ICP in experimental conditions.We retrospectively analysed experimental material collected previously. Three physiological manoeuvres were studied in 29 New Zealand white rabbits: lumbar infusion with an infusion rate ≤0.2 mL/min to induce mild intracranial hypertension (n = 43), sympathetic blockade to induce arterial hypotension (n = 19), and modulation of the ventilator tidal volume, simultaneously influencing arterial carbon dioxide partial pressure (PaCO2) to induce hypocapnia or hypercapnia (n = 17). We investigated whether the slope of the pulse amplitude (AMP)-ICP line depended on PaCO2 and arterial blood pressure (ABP) changes.We found a linear correlation between AMP-ICP and ICP with positive slope. Regression of slope against mean ABP showed a negative dependence (p = 0.03). In contrast, the relationship between slope and PaCO2 was positive, although not reaching statistical significance (p = 0.18).The slope of amplitude-pressure line is strongly modulated by systemic vascular variables and therefore should be taken as a descriptor of cerebrospinal fluid dynamics with great care.

Single Center Experience in Cerebrospinal Fluid Dynamics Testing.

Normal pressure hydrocephalus is more complex than a simple disturbance of the cerebrospinal fluid (CSF) circulation. Nevertheless, an assessment of CSF dynamics is key to making decisions about shunt insertion, shunt malfunction, and for further management if a patient fails to improve. We summarize our 25 years of single center experience in CSF dynamics assessment using pressure measurement and analysis. 4473 computerized infusion tests have been performed. We have shown that CSF infusion studies are safe, with incidence of infection at less than 1%. Raised resistance to CSF outflow positively correlates (p < 0.014) with improvement after shunting and is associated with disturbance of cerebral blood flow and its autoregulation (p < 0.02). CSF infusion studies are valuable in assessing possible shunt malfunction in vivo and for avoiding unnecessary revisions. Infusion tests are safe and provide useful information for clinical decision-making for the management of patients suffering from hydrocephalus.

Increasing Intracranial Pressure After Head Injury: Impact on Respiratory Oscillations in Cerebral Blood Flow Velocity.

Experiments have shown that closed-box conditions alter the transmission of respiratory oscillations (R waves) to organ blood flow already at a marginal pressure increase. How does the increasing intracranial pressure (ICP) interact with R waves in cerebral blood flow after head injury (HI)?Twenty-two head-injured patients requiring sedation and mechanical ventilation were monitored for ICP, Doppler flow velocity (FV) in the middle cerebral arteries, and arterial blood pressure (ABP). The analysis included transfer function gains of R waves (9-20 cpm) from ABP to FV, and indices of pressure-volume reserve (RAP) and autoregulation (Mx). Increasing ICP has dampened R-wave gains from day 1 to day 4 after HI in all patients. A large impact (ΔGain /ΔICP right: 0.14 ± 0.06; left: 0.18 ± 0.08) was associated with exhausted reserves (RAP ≥0.85). When RAP was <0.85, rising ICP had a lower impact on R-wave gains (ΔGain /ΔICP right: 0.05 ± 0.02; left: 0.06 ± 0.04; p < 0.05), but increased the pulsatility indices (right: 1.35 ± 0.55; left: 1.25 ± 0.52) and Mx indices (right: 0.30 ± 0.12; left: 0.28 ± 0.08, p < 0.05). Monitoring of R waves in blood pressure and cerebral blood flow velocity has suggested that rising ICP after HI might have an impact on cerebral blood flow directly, even before autoregulation is impaired.

Waveform Analysis of Intraspinal Pressure After Traumatic Spinal Cord Injury: An Observational Study (O-64).

Following a traumatic brain injury (TBI), intracranial pressure (ICP) increases, often resulting in secondary brain insults. After a spinal cord injury, here the cord may be swollen, leading to a local increase in intraspinal pressure (ISP). We hypothesised that waveform analysis methodology similar to that used for ICP after TBI may be applicable for the monitoring of patients with spinal cord injury.An initial cohort of 10 patients with spinal cord injury, as presented by the first author at a meeting in Cambridge in May 2012, were included in this observational study. The whole group (18 patients) was recently presented in the context of clinically oriented findings (Werndle et al., Crit Care Med, 42(3):646-655, 2014, PMID: 24231762). Mean pressure, pulse and respiratory waveform were analysed along slow vasogenic waves.Slow, respiratory and pulse components of ISP were characterised in the time and frequency domains. Mean ISP was 22.5 ± 5.1, mean pulse amplitude 1.57 ± 0.97, mean respiratory amplitude 0.65 ± 0.45 and mean magnitude of slow waves (a 20-s to 3-min period) was 3.97 ± 3.1 (all in millimetres of mercury). With increasing mean ISP, the pulse amplitude increased in all cases. This suggests that the ISP signal is of a similar character to ICP recorded after TBI. Therefore, the methods of ICP analysis can be helpful in ISP analysis.

Phase-shift between arterial flow and ICP pulse during infusion test.

BACKGROUND: The dynamic relationship between pulse waveform of intracranial pressure (ICP) and transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) may contain information about cerebrospinal compliance. This study investigated the possibility by focusing on the phase shift between fundamental harmonics of CBFV and ICP. METHODS: Thirty-seven normal pressure hydrocephalus patients (20 men, mean age 58) underwent the cerebrospinal fluid (CSF) infusion tests. The infusion was performed via pre-implanted Ommaya reservoir. The TCD FV was recorded in the middle cerebral artery. Resulting continuous ICP and pressure-volume (PV) signals were analyzed by ICM+ software. RESULTS: In initial stage of the CSF infusion, the phase shift was negative (median value = -11°, range = +60 to -117). There was significant inverse association of phase shift with brain elasticity (R = -0.51; p = 0.0009). In all tests, phase shift consistently decreased during gradual elevation of ICP (p = 0.00001). Magnitude of decrease in phase shift was inversely related to the peak-to-peak amplitude of ICP pulse waveform at a baseline (R = -0.51; p = 0.001). CONCLUSIONS: Phase shift between fundamental harmonics of ICP and TCD waveforms decreases during elevation of ICP. This is caused by an increase of time delay between systolic peak of flow velocity wave and ICP pulse.

How does moderate hypocapnia affect cerebral autoregulation in response to changes in perfusion pressure in TBI patients?

In traumatic brain injury, the hypocapnic effects on blood pressure autoregulation may vary from beneficial to detrimental. The consequences of moderate hypocapnia (HC) on the autoregulation of cerebral perfusion pressure (CPP) have not been monitored so far.Thirty head injured patients requiring sedation and mechanical ventilation were studied during normocapnia (5.1 ± 0.4 kPa) and moderate HC (4.4 ± 3.0 kPa). Transcranial Doppler flow velocity (Fv) of the middle cerebral arteries (MCA), invasive arterial blood pressure, and intracranial pressure were monitored. CPP was calculated. The responsiveness of Fv to slow oscillations in CPP was assessed by means of the moving correlation coefficient, the Mx autoregulatory index. Hypocapnic effects on Mx were increasing with its deviation from normal baseline (left MCA: R (2) = 0.67; right MCA: R (2) = 0.51; p < 0.05). Mx indicating normal autoregulation (left: -0.23 ± 0.23; right: -0.21 ± 0.24) was not significantly changed by moderate HC. Impaired Mx autoregulation, however, (left: 0.37 ± 0.13; right: 0.33 ± 0.26) was improved (left: 0.12 ± 0.25; right: -0.0003 ± 0.19; p < 0.01) during moderate HC. Mx was adjusted to normal despite no significant change in CPP levels. Our study showed that short-term moderate HC may optimize the autoregulatory response to spontaneous CPP fluctuations with only a small CPP increase. Patients with impaired autoregulation seemed to benefit the most.

Slow vasogenic fluctuations of intracranial pressure and cerebral near infrared spectroscopy--an observational study.

BACKGROUND/PURPOSE: Increased slow-wave activity in intracranial pressure (ICP) signifies an exhausted cerebrospinal compensatory reserve across a range of conditions. In this study, we attempted to describe synchronisation between slow waves of ICP and of near-infrared spectroscopy (NIRS) variables during controlled elevation of ICP. METHOD: Nineteen patients presenting with symptomatic hydrocephalus underwent a Computerised Infusion Test. NIRS-derived indices, ICP and arterial blood pressure (ABP) were recorded simultaneously. FINDINGS: ICP increased from 9.3 (6.0) mmHg to a 17.1 (8.9) mmHg during infusion. Slow waves in ICP were accompanied by concurrent waves in each NIRS variable (including deoxygenated haemoglobin (Hb) and oxygenated haemoglobin (HbO2)) with a mean coherence of >0.7 and no significant phase shift. In the same bandwidth (0.3-1.8 min(-1)), ABP fluctuations occurred with a coherence of 0.77 and phase lead of 40° with respect to ICP. The power of ICP slow waves increased significantly during infusion plateau with a corresponding increase in power of Hb waves. CONCLUSIONS: Slow fluctuations in cerebral oximetry as detected by NIRS coincide with and are implicated in the origin of ICP slow waves and increases during periods of exhausted cerebrospinal compensatory reserve. NIRS may be used as a non-invasive marker of increased ICP slow waves (and therefore reduced CSF compensatory reserve).

An assessment of dynamic autoregulation from spontaneous fluctuations of cerebral blood flow velocity: a comparison of two models, index of autoregulation and mean flow index.

BACKGROUND: Various methods of assessment of cerebral autoregulation, using spontaneous slow fluctuations of blood flow velocity (FV), arterial blood pressure, and cerebral perfusion pressure, have been used in clinical practice. We studied the association between the dynamic index of autoregulation (ARI) and time correlation index (mean flow index, Mx) in a group of patients after head injury. METHODS: Fifty head-injured patients of an average age of 31 yr, sedated, paralyzed, and ventilated (mild hypocapnia) with continuous monitoring of arterial blood pressure and intracranial pressure were studied. Cerebral blood FV was monitored daily for 3 days after injury during periods that were free from interventions (e.g., suctioning). Digitally recorded data were analyzed retrospectively. ARI was calculated as a coefficient graded from 0 (absence of autoregulation) to 9 (strongest autoregulation), describing a dynamic model of autoregulation. Mx was calculated as the correlation coefficient between 40 consecutive 6-s averages of FV and cerebral perfusion pressure and then averaged over the whole recording period. ARI and Mx values, assessed during the first 3 days after injury, were averaged for each patient. RESULTS: ARI and Mx showed moderately strong mutual linear relationship with correlation r = -0.62; P = 0.0001. Both indices correlated with outcome, indicating worse autoregulation in patients achieving unfavorable outcome. CONCLUSION: ARI and Mx agree relatively well in head-injured patients. Autoregulation affects outcome after head injury.

Cerebrovascular reactivity and autonomic drive following traumatic brain injury.

INTRODUCTION: The autonomic nervous system exerts tonic control on cerebral vessels, which in turn determine the autoregulation of cerebral blood flow. We hypothesize that the impairment of cerebral autoregulation following traumatic brain injury might be related to the acute failure of the autonomic system. METHODS: This prospective, observational study included patients with severe traumatic brain injury requiring mechanical ventilation and invasive monitoring of intracranial pressure (ICP) and arterial blood pressure (ABP). Pressure reactivity index (PRx), a validated index of cerebrovascular reactivity, was continuously monitored using bedside computers. Autonomic drive was assessed by means of heart rate variability (HRV) using frequency domain analysis. FINDINGS: Eighteen TBI patients were included in the study. Cerebrovascular reactivity impairment (PRx above 0.2) and autonomic failure (low spectral power of HRV) are significantly and independently associated with fatal outcome (P = 0.032 and P < 0.001, respectively). We observed a significant correlation between PRx and HRV spectral power (P < 0.001). The high frequency component of HRV (HF, 0.15-0.4Hz) can be used to predict impaired autoregulation (PRx > 0.2), although sensitivity and specificity are low (ROC AUC = 0.67; P = 0.001). CONCLUSION: Following traumatic brain injury, autonomic failure and cerebrovascular autoregulation impairment are both associated with fatal outcome. Impairment of cerebrovascular autoregulation and autonomic drive are interdependent phenomena. With some refinements, HRV might become a tool for screening patients at risk for cerebral autoregulation derangement following TBI.

Is there a direct link between cerebrovascular activity and cerebrospinal fluid pressure-volume compensation?

BACKGROUND AND PURPOSE: Cerebral blood flow is coupled to brain metabolism by means of active modulation of cerebrovascular resistance. This homeostatic vasogenic activity is reflected in slow waves of cerebral blood flow velocities (FV) which can also be detected in intracranial pressure (ICP). However, effects of increased ICP on the modulation of cerebral blood flow are still poorly understood. This study focused on the question whether ICP has an independent impact on slow waves of FV within the normal cerebral perfusion pressures range. METHODS: Twenty patients presenting with communicating hydrocephalus underwent a diagnostic intraventricular constant-flow infusion test. Blood flow velocities in the middle cerebral artery and posterior cerebral arteries were measured using Transcranial Doppler. Pulsatility index, FV variability of slow vasogenic waves (3 to 9 bpm), ICP, and arterial blood pressure were simultaneously monitored. RESULTS: During the test, ICP increased from a baseline of 11 (6) mm Hg to a plateau value of 21 (6) mm Hg (P=0.00005). Although the infusion did not induce significant changes in cerebral perfusion pressures, FV, pulsatility index, or index of autoregulation, the magnitude of FV vasogenic waves at plateau became inversely correlated to ICP (middle cerebral artery: r=-0.58, P<0.01; posterior cerebral arteries: r=-0.54, P<0.01). CONCLUSIONS: This study shows that even moderately increased ICP can limit the modulation of cerebral blood flow in both vascular territories within the autoregulatory range of cerebral perfusion pressures. The exhaustion of cerebrospinal fluid volume buffering reserve during infusion studies elicits a direct interaction between the cerebrospinal fluid space and the cerebrovascular compartment.

Noninvasive evaluation of dynamic cerebrovascular autoregulation using Finapres plethysmograph and transcranial Doppler.

BACKGROUND AND PURPOSE: Mx is an index of cerebrovascular autoregulation. It is calculated as the correlation coefficient between slow spontaneous fluctuations of cerebral perfusion pressure (cerebral perfusion pressure=arterial blood pressure-intracranial pressure) and cerebral blood flow velocity. Mx can be estimated noninvasively (nMxa) with the use of a finger plethysmograph arterial blood pressure measurement instead of an invasive cerebral perfusion pressure measurement. We investigated the agreement between nMxa and the previously validated index Mx. METHODS: The study included 10 head-injured adults. Intracranial pressure was monitored with a parenchymal probe. Arterial blood pressure was monitored simultaneously with an arterial catheter and with the Finapres plethysmograph. Flow velocity in the middle cerebral artery was measured bilaterally with transcranial Doppler. Mx and nMxa were computed in both hemispheres, and asymmetry of autoregulation was calculated. RESULTS: Ninety-six measures of Mx and nMxa were obtained (48 for each side) in 10 patients. Mx correlated with nMxa (R=0.755, P<0.001; 95% agreement=+/-0.36; bias=0.01). Asymmetry in autoregulation assessed with Mx correlated significantly with asymmetry estimated with nMxa (R=0.857, P<0.0001; 95% agreement=+/-0.26; bias=-0.03). CONCLUSIONS: The noninvasive index of autoregulation nMxa correlates with Mx and is sensitive enough to detect autoregulation asymmetry. nMxa is proposed as a practical tool to assess cerebral autoregulation in patients who do not require invasive monitoring.

Continuous time-domain analysis of cerebrovascular autoregulation using near-infrared spectroscopy.

BACKGROUND AND PURPOSE: Assessment of autoregulation in the time domain is a promising monitoring method for actively optimizating cerebral perfusion pressure (CPP) in critically ill patients. The ability to detect loss of autoregulatory vasoreactivity to spontaneous fluctuations in CPP was tested with a new time-domain method that used near-infrared spectroscopic measurements of tissue oxyhemoglobin saturation in an infant animal model. METHODS: Piglets were made progressively hypotensive over 4 to 5 hours by inflation of a balloon catheter in the inferior vena cava, and the breakpoint of autoregulation was determined using laser-Doppler flowmetry. The cerebral oximetry index (COx) was determined as a moving linear correlation coefficient between CPP and INVOS cerebral oximeter waveforms during 300-second periods. A laser-Doppler derived time-domain analysis of spontaneous autoregulation with the same parameters (LDx) was also determined. RESULTS: An increase in the correlation coefficient between cerebral oximetry values and dynamic CPP fluctuations, indicative of a pressure-passive relationship, occurred when CPP was below the steady state autoregulatory breakpoint. This COx had 92% sensitivity (73% to 99%) and 63% specificity (48% to 76%) for detecting loss of autoregulation attributable to hypotension when COx was above a threshold of 0.36. The area under the receiver-operator characteristics curve for the COx was 0.89. COx correlated with LDx when values were sorted and averaged according to the CPP at which they were obtained (r=0.67). CONCLUSIONS: The COx is sensitive for loss of autoregulation attributable to hypotension and is a promising monitoring tool for determining optimal CPP for patients with acute brain injury.

Slow oscillations in middle cerebral artery cerebral blood flow velocity and aging.

OBJECTIVE: A recent study using near infrared spectroscopy (NIRS) showed that low frequency oscillations of regional cerebral blood flow (CBF) decline with age. Using transcranial Doppler ultrasound (TCD), it is possible to monitor similar fluctuations in cerebral blood velocity (CBV) in basal cerebral vessels. Such oscillations have been used widely in the assessment of cerebral autoregulation. We postulated that it should be possible to observe similar age related reductions in the amplitude of slow waves recorded using TCD. METHODS: We studied 187 patients with head injury, who were admitted to Addenbrooke's Neuro Critical Care unit between 1992 and 1998. Intermittent recordings of CBV were undertaken using TCD, which were subsequently analysed using software developed in-house. Power spectra were computed in the very low frequency (VLF: 0.01-0.05 Hz) and low frequency (LF: 0.07-0.11 Hz) ranges for all signals and a regression analysis was performed to assess the correlation between power in each frequency band and age. RESULTS: No significant correlation was found between VLF or LF power and age (VLF: r=0.037; p=0.63; LF: r=-0.05, p=0.517). DISCUSSION: While remaining cogniscent of the complex nature of our patient group, we find that age dependent reductions in CBF oscillations seen using NIRS do not translate to recordings of CBV in the middle cerebral artery in patients with head injury.

Pulse pressure waveform in hydrocephalus: what it is and what it isn't.

OBJECT: Apart from its mean value, the pulse waveform of intracranial pressure (ICP) is an essential element of pressure recording. The authors reviewed their experience with the measurement and interpretation of ICP pulse amplitude by referring to a database of recordings in hydrocephalic patients. METHODS: The database contained computerized pressure recordings from 2100 infusion studies (either lumbar or intraventricular) or overnight ICP monitoring sessions in patients suffering from hydrocephalus of various types (both communicating and noncommunicating), origins, and stages of management (shunt or no shunt). Amplitude was calculated from ICP waveforms by using a spectral analysis methodology. RESULTS: The appearance of a pulse waveform amplitude is positive evidence of a technically correct recording of ICP and helps to distinguish between postural and vasogenic variations in ICP. Pulse amplitude is significantly correlated with the amplitude of cerebral blood flow velocity (R = 0.4, p = 0.012) as assessed using Doppler ultrasonography. Amplitude is positively correlated with a mean ICP (R = 0.21 in idiopathic normal-pressure hydrocephalus [NPH]; number of cases 131; p < 0.01) and resistance to cerebrospinal fluid outflow (R = 0.22) but does not seem to be correlated with cerebrospinal elasticity, dilation of ventricles, or severity of hydrocephalus (NPH score). Amplitude increases slightly with age (R = 0.39, p < 0.01; number of cases 46). A positive association between pulse amplitude and increased ICP during an infusion study is helpful in distinguishing between hydrocephalus and predominant brain atrophy. A large amplitude is associated with a good outcome after shunting (positive predictive power 0.9), whereas a low amplitude has no predictive power in outcome prognostication (0.5). Pulse amplitude is reduced by a properly functioning shunt. CONCLUSIONS: Proper recording, detection, and interpretation of ICP pulse waveforms provide clinically useful information about patients suffering from hydrocephalus.

Age, intracranial pressure, autoregulation, and outcome after brain trauma.

OBJECT: The object of this study was to investigate whether a failure of cerebrovascular autoregulation contributes to the relationship between age and outcome in patients following head injury. METHODS: Data obtained from continuous bedside monitoring of intracranial pressure (ICP), arterial blood pressure (ABP), and cerebral perfusion pressure (CPP = ABP - ICP) in 358 patients with head injuries and intermittent monitoring of transcranial Doppler blood flow velocity (FV) in the middle cerebral artery in 237 patients were analyzed retrospectively. Indices used to describe cerebral autoregulation and pressure reactivity were calculated as correlation coefficients between slow waves of systolic FV and CPP (autoregulation index [ARI]) and between ABP and ICP (pressure reactivity index [PRI]). Older patients had worse outcomes after brain trauma than younger patients (p = 0.00001), despite the fact that the older patients had higher initial Glasgow Coma Scale scores (p = 0.006). When age was considered as an independent variable, it appeared that ICP decreased with age (p = 0.005), resulting in an increasing mean CPP (p = 0.0005). Blood FV was not dependent on age (p = 0.58). Indices of autoregulation and pressure reactivity demonstrated a deterioration in cerebrovascular control with advancing age (PRI: p = 0.003; ARI: p = 0.007). CONCLUSIONS: An age-related decline in cerebrovascular autoregulation was associated with a relative deterioration in outcome in elderly patients following head trauma.

Traumatic brain injury: increasing ICP attenuates respiratory modulations of cerebral blood flow velocity.

In vitro experiments have suggested that respiratory oscillations (R waves) in cerebral blood flow velocity are reduced as soon as the intracranial pressure-volume reserve is exhausted. Could R waves hence, provide indication for increasing ICP after traumatic brain injury (TBI)? On days 1 to 4 after TBI, 22 sedated and ventilated patients were monitored for intracranial pressure (ICP) in brain parenchyma, Doppler flow velocity (FV) in the middle cerebral arteries (MCA), and arterial blood pressure (ABP). The analysis included the transfer function gains of R waves (respiratory rate of 9-20 cpm) between ABP and FV (GainFv) as well as between ABP and ICP (GainICP). Also, the index of the intracranial pressure-volume reserve (RAP) was calculated. The rise of ICP (day 1: 14.10 ± 6.22 mmHg; to day 4: 29.69 ± 12.35 mmHg) and increase of RAP (day 1: 0.72 ± 0.22; to day 4: 0.85 ± 0.18) were accompanied by a decrease of GainFv (right MCA; day 1: 1.78 ± 1.0; day 4: 0.84 ± 0.47; left MCA day 1: 1.74 ± 1.10; day 4: 0.86 ± 0.46; p < 0.01) but no significant change in GainICP day 1: 1.50 ± 0.77; day 4: 1.15 ± 0.47; p = 0.07). The transfer of ventilatory oscillations to the intracerebral arteries after TBI appears to be dampened by increasing ICP and exhausted intracranial pressure-volume reserves. Results warrant prospective studies of whether respiratory waves in cerebral blood flow velocity may anticipate intracranial hypertension non-invasively.

Relationship between flow-metabolism uncoupling and evolving axonal injury after experimental traumatic brain injury.

Blood flow-metabolism uncoupling is a well-documented phenomenon after traumatic brain injury, but little is known about the direct consequences for white matter. The aim of this study was to quantitatively assess the topographic interrelationship between local cerebral blood flow (LCBF) and glucose metabolism (LCMRglc) after controlled cortical impact injury and to determine the degree of correspondence with the evolving axonal injury. LCMRglc and LCBF measurements were obtained at 3 hours in the same rat from 18F-fluorodeoxyglucose and 14C-iodoantipyrine coregistered autoradiographic images, and compared to the density of damaged axonal profiles in adjacent sections and in an additional group at 24 hours using beta-amyloid precursor protein (beta-APP) immunohistochemistry. LCBF was significantly reduced over the ipsilateral hemisphere by 48 +/- 15% compared with sham-controls, whereas LCMRglc was unaffected, apart from foci of elevated LCMRglc in the contusion margin. Flow-metabolism was uncoupled, indicated by a significant 2-fold elevation in the LCMRglc/LCBF ratio within most ipsilateral structures. There was a significant increase in beta-APP-stained axons from 3 to 24 hours, which was negatively correlated with LCBF and positively correlated with the LCMRglc/LCBF ratio at 3 hours in the cingulum and corpus callosum. Our study indicates a possible dependence of axonal outcome on flow-metabolism in the acute injury stage.

Changes in cerebral blood flow during cerebrospinal fluid pressure manipulation in patients with normal pressure hydrocephalus: a methodological study.

The combination of cerebral blood flow measurement using (15)O-water positron emission tomography with magnetic resonance coregistration and CSF infusion studies was used to study the global and regional changes in CBF with changes in CSF pressure in 15 patients with normal pressure hydrocephalus. With increases in CSF pressure, there was a variable increase in arterial blood pressure between individuals and global CBF was reduced, including in the cerebellum. Regionally, mean CBF decreased in the thalamus and basal ganglia, as well as in white matter regions. These reductions in CBF were significantly correlated with changes in the CSF pressure and with proximity to the ventricles. A three-dimensional finite-element analysis was used to analyze the effects on ventricular size and the distribution of stress during infusion. To study regional cerebral autoregulation in patients with possible normal pressure hydrocephalus, a sensitive CBF technique is required that provides absolute, not relative normalized, values for regional CBF and an adequate change in cerebral perfusion pressure must be provoked.

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.

Normal pressure hydrocephalus and cerebral blood flow: a PET study of baseline values.

Regional cerebral blood flow (CBF) was studied with O(15)-water positron emission tomography and anatomic region-of-interest analysis on co-registered magnetic resonance in patients with idiopathic (n = 12) and secondary (n = 5) normal pressure hydrocephalus (NPH). Mean CBF was compared with values obtained from healthy volunteers (n = 12) and with clinical parameters. Mean CBF was significantly decreased in the cerebrum and cerebellum of patients with NPH. The regional analysis demonstrated that CBF was reduced in the basal ganglia and the thalamus but not in white matter regions. The results suggest that the role of the basal ganglia and thalamus in NPH may be more prominent than currently appreciated. The implications for theories regarding the pathogenesis of NPH are discussed.