Abstracts of the 8th International Conference on Xenon CT and Related Cerebral Blood Flow Techniques: cerebral blood flow and brain metabolic imaging in clinical practice

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Quantitative estimation of low CBF value by lambda and flow rate constant obtained by xenon-enhanced CT under various ischaemic conditions

M. Ohashi¹, M. Matsuda¹ & S. Sase² (¹Department of Neurosurgery, Shiga University of Medical Science, and ²Anzai Medical Co. Ltd., Shiga)

Background: Quantitative measurement of regional cerebral blood flow (rCBF) is not always accurate in ischaemia. The rCBF obtained by stable xenon-enhanced CT (XeCT) is calculated using the modified Kety–Schmidt equation that integrates the time-dependent concentrations of xenon in the arterial blood and the brain tissue and the partition coefficient (lambda, λ). Blood flow rate (f) is a product of flow rate constant (K) multiplied by λ. Since the ischaemic areas with low rCBF are not uniform in terms of K and λ, we analysed the low rCBF in relation to λ and K in various ischaemic conditions.

Methods: Low rCBFs were observed in 20 patients. XeCT was performed with a 5-min wash-in protocol. After base scan the patient started to inhale a mixture of gas (28% xenon, 30 – 50% oxygen and balance air) provided by the system (AZ-725, Anzai Medical) and underwent CT scans every 1 min for 5-min inhalation period.

Results: In acute stroke cases, the ischaemic areas with lower λ (<0.2) well predicted the eventual infarction even though postreperfusion rCBF increased to above 23 ml/100 g/min from 11 ml/100 g/min. However, the other areas where the λ remained in 1.0 – 2.0 did not go into infarct on later CT scan/MR imaging. Extremely low K (<0.07) and elevated λ (>2.5) were observed in the area where rCBF was relatively low (18∼24 ml/100 g/min) in patients with dural arteriovenous fistula or during balloon test occlusion.

Conclusions: (1) Lower λ should more reliably predict the fate of the lesions in acute ischaemia. (2) Extremely low K and elevated λ would indicate low perfusion due to congestion or insufficient collateral circulation in the affected area.

Preliminary study of decrease of radiation exposure in xenon CT cerebral blood flow examination in Japan

T. Yamashita^1,4, M. Urakawa^1,4, H. Yasuda^1,4, S. Nogawa^2,5, T. Dembo^3,6, M. Honda^1,7 & S. Sase⁸ (Departments of ¹Neurosurgery, ²Internal Medicine, and ³Neurology, ⁴Yamaguchi Grand Medical Center, ⁵Tokyo Dental College Ichikawa General Hospital, ⁶Keio University, ⁷Critical Care Unit, Toho University Omori Medical Center, and ⁸Anzai Medical Co., Ltd)

Background: Diagnostic X-rays contributed to 0.6% of the cumulated risk to become cancer in the UK.[1] The risk is 3.2% in Japan. Xenon CT has to scan the same slice many times, and produces much radiation exposure. We investigated reduction of radiation exposure in xenon CT.

Methods: We did questionnaire investigation in Japanese 202 institutions in 3 months since December, 2004. The investigation item included the number of scan slices, the number of scans per slice, the X-ray tube voltage (kVp), tube current (mAs) and the CTDIw. We studied the influence that decrease of number of scans gave to CBF value. Furthermore, we scanned three kinds of iodine solutions under a different condition of kVp and mAs, and compared signal/noise ratio (S/N) among the different conditions.

Results: The number of scan slices was 2.6 ± 1.3 (mean ± SD). The number of scans per one slice was 9.3 ± 1.7. The tube voltage was from 80 to 130 kVp, 120 kVp in most institutions. The tube current was 347 ± 128 mAs. The radiation exposure was 1108.3 ± 874.4 mGy. The decrease of number of scans resulted in CBF increase of 3 – 5 ml/100 mg/min. If the current was bigger, S/N of an image was better. In terms of tube voltage, the relative maximum value of S/N was found between 100 and 120 kVp.

Conclusions: Among Japanese institutions, number of scan slices and number of scans per one slice were various. Making of a guideline is necessary for reduction of radiation exposure. For reduction of radiation exposure, we have to reconsider a scan condition.

Effects of head motion on heart rate variability in patients undergoing xenon-enhanced computed tomography

M. Sesay, D. Gense de Beaufort, V. Sesay & V. Dousset (Department of Anaesthesiology and Neuroradiology, Pellegrin University Hospital, Bordeaux, France)

Background: Head motion is a major setback to the accuracy of cerebral blood flow measured by a variety neuroimaging procedures.[1] In patients undergoing xenon-enhanced computed tomography (XeCT), the anaesthetic effects of xenon and the apprehension for the facemask are important triggers of head motion. Heart rate variability (HRV) is a non-invasive marker of the autonomic responses to various stimuli including anaesthesia and anxiety. The aim of this study was to determine its responses to head motion during XeCT.

Methods: After institutional review board approval and informed consent, HRV was assessed in 25 patients undergoing XeCT (DDP, Texas, USA). HRV was calculated from the ECG R-R interval using the maximum entropy method (Suwa Trust, Tokyo, Japan). The low frequency (LF: 0.04 – 0.15 Hz) and high frequency (HF: 0.15 – 0.4 Hz) spectra were associated with the sympathetic and parasympathetic activities, respectively.[2] These parameters were noted before (baseline) and during inhalation. The motion check algorithm of the XeCT software was used to confirm head motion.

Results: Slight head motion was depicted in nine patients and agitation in two. The mean LF/HF ratio in of these 11 patients was more than 1 and significantly higher during inhalation than the baseline value. The other patients had LF/HF ratios <1.

Conclusions: Head motion has a specific HRV profile in patient undergoing XeCT. If confirmed by other studies, HRV could be complementary to the clinical monitoring of patients in this procedure.

Head holder using negative pressure bag packed with plastic beads in xenon CT CBF study, and its technical note

Y. Araki, H. Nokura & T. Itoh (Department of Neurosurgery, Inuyama Chuo Hospital, Aichi, Japan)

Background: To obtain high quality CBF maps, it is essential that the head of patients should be reliably fixed during CBF examinations. Employing analysis of CBF confidence maps, we investigated the usefulness of a head holder using a negative pressure bag packed with plastic beads in a xenon CT CBF study.[1]

Methods: A total of 272 consecutive patients for the CBF study were enrolled and classified into three groups: 88 patients with a negative pressure bag (M group), 87 patients with an air pillow (A group) and 97 patients with a sponge pillow (S group). The degree of effect of head movements on the CBF measurement in each patient was expressed as a confidence value (mean of the confidence values at one CT slice).

Results: The mean of confidence value in the M group (0.461) was statistically lower than in the A group (0.866) and that in the S group (1.043).

Conclusions: These findings showed that the head holder using a negative pressure bag was useful for obtaining CBF maps of high quality in a xenon CT CBF study. We will demonstrate the usage of our pillow at the meeting.

Algorithms to estimate cerebral blood flow (CBF) and cerebral blood volume (CBV) by the near infrared spectroscopy indocyanine green dye dilution method and normal values in healthy volunteers

R. Mudra¹, P. Niederer¹ & E. Keller² (¹Institute of Biomedical Engineering, and ²Neurointensive Care Unit, Department of Neurosurgery; University Hospital Zurich)

Background: Development of a non-invasive measurement method for regional cerebral blood flow (CBF), easy to perform at the bedside in the intensive care unit.

Methods: To determine the cerebral haemodynamics with near infrared spectroscopy (NIRS) indocyanine green (ICG) dye dilution, an algorithm has been developed to analyse the optical density (OD) signals. Bilateral monitoring of the passage of the tracer ICG within brain vessels, allows estimating regional values for mean transit time (mtt), cerebral blood volume (CBV) and CBF. In an iterative process the monitored transfer function is fitted with different lognorm functions. The best approximation allows the determination of the mtt in the optical segment. Additionally, ICG concentrations within the illuminated tissue segments are estimated by an exponential extrapolation. The ICG concentration in the arterial inflow is estimated by the quotient of injected ICG and total blood volume, which is calculated in relation to the body weight. These two ICG concentrations are used to estimate the CBVs within illuminated regions. Finally, these calculated CBVs are used together with the mtts of the human brain system to determine the CBF. In parallel the oxygen metabolism is determined.

Results: In 10 healthy volunteers normal values for the NIRS ICG dye dilution method are estimated to be for mtt min = 5.1 to max = 16.3 s (median 9.4 s), for CBV min = 1.7 to max = 4.3 ml/100 g (median 3.5 ml/100 g) and for CBF min = 4.3 to max =50.1 ml/100 g/min (median 17 ml/100 g/min).

Conclusions: Calculated CBV and CBF are in accordance with results of previous NIRS[7][2],[3] and PET studies.[4]

Measurement of cerebral blood flow with indocyanine green and NIRS, before and after the administration of acetazolamide

T. S. Leung¹, I. Tachtsidis¹, M. Tisdall², M. Smith², C. E. Elwell¹ & D. T. Delpy¹ (¹Department of Medical Physics & Bioengineering, University College London, and ²Department of Neuroanaesthesia, The National Hospital for Neurology and Neurosurgery, London, UK)

Background: This study aims to investigate the potential of using near infrared spectroscopy (NIRS) with indocyanine green (ICG) bolus tracking to measure cerebral blood flow (CBF). To induce an increase of CBF, acetazolamide (ACZ) has been administered intravenously.

Methods: Ten healthy volunteers (mean 29.6 years) participated in the study. Three rapid intravenous injections (IV) of ICG (0.1 mg/kg) were given in a peripheral vein of the left arm at approximately 15-min intervals. Following the 3rd ICG injection, ACZ (1 g) was administered by slow IV injection and, after 20 min, a 4th ICG injection was given. A NIRS spectrometer (NIRO 300, Hamamatsu) was used to measure the tissue ICG concentration (ICGtis) with optodes placed 5 cm apart on the forehead. A differential path length factor of 6.26 was used. The arterial ICG concentration (ICGart) was measured by a pulse dye densitometer (DDG2001, Nihon Kohden Co.) using a nasal probe. CBF was calculated using the impulse residue function by deconvolving the ICGtis with ICGart. Middle cerebral artery blood flow velocity (Vmca) was measured in the basal right middle cerebral artery using a transcranial Doppler (Pioneer Nicolet Biomedical Inc).

Results: The group mean difference in Vmca before and after ACZ was 49 ± 20.6%. The mean estimated CBF was 4.7 ± 0.8 ml/100 g/min (before ACZ) and 4.8 ± 1.2 ml/100 g/min (after ACZ). The mean difference in CBF before and after ACZ was 0.09 ± 1.33 ml/100 g/min. The increase in CBF after ACZ was not statistically significant.

Conclusions: Estimated CBF was lower than expected and can be attributed to the influence of the extracerebral layers. The results indicate that this method cannot reliably measure an increase of CBF after ACZ injection.

Quantification of cerebral blood flow using near infrared spectroscopy and indocyanine green

P. G. Al-Rawi¹, T. Leung², P. Smielewski¹, D. T. Delpy² & P. J. Kirkpatrick¹ (¹University Department of Neurosurgery, Cambridge, and ²Department of Medical Physics, University College London, UK)

Introduction: Early intervention remains the key to acute ischaemic therapy in many conditions affecting the brain. There is currently no practical method for accurately measuring CBF rapidly, repeatedly and non-invasively at the bedside. This study aims to develop an algorithm for accurate CBF assessment using near infrared spectroscopy (NIRS) and indocyanine green (ICG) dye dilution.

Methodology:

By combining NIRS and ICG, regional CBF can be estimated by application of Fick's principle. Arterial ICG concentration (ICGart) was measured by dye densitometry (LiMon. Pulsion) and ICG tissue concentration (ICGtis) with NIRO 300 (Hamamatsu Photonics). Venous injections of 0.5 mg/kg ICG were performed. The appearance of ICG in the optical field and dye dilution curves was recorded and ICG concentrations calculated from changes in optical density. CBF is calculated by deconvolving ICGtis with ICGart. By using calculated ICGtis based on spatially resolved spectroscopy we aim to improve accuracy of the estimated CBF.

Patients:

Following informed assent, NIRS ICG measurements were performed in 14 patients (40 CBF estimations) suffering severe SAH. Nine patients also underwent xenon CT (XeCT).

Results: Initial results show the calculated CBF (mean 11.9 ml/100 g/min, SD 3.0; n = 3) is lower than expected for this group of patients, and lower than obtained by XeCT (mean 28.4 ml/100 g/min, SD 1.76). Comparison of these results with XeCT is on-going and work in progress to correct the algorithm accordingly.

Discussion: Bedside assessment of CBF could become a key tool in early investigation of neurovascular patients. This pilot data shows the potential for this analysis method to provide a bedside measurement of CBF. This presentation will discuss the sensitivity, accuracy and reproducibility of both the technique and the newly derived algorithm. If proven, this method would be more accessible and cheaper than current techniques.

Brain oxygenation and blood volume changes during routine neurocritical care measured using near infra-red spectroscopy (NIRS)

A. Dalton¹, M. Thorniley² & C. Childs³ (¹Medical student, ²School of Chemical Engineering and Analytical Science, and ³Department of Neurosurgery, University of Manchester, UK)

Background: Noradrenaline (NA) is commonly administered to patients with traumatic brain injury (TBI) to optimise brain perfusion. In the acute phase of head injury, NA may have a direct effect on cerebral metabolism and blood flow. The objectives of this study are to investigate the effect of NA on regional cerebral oxygenation and haemodynamics measured by NIRS. It is essential first to determine the effect of routine neurocritical care on NIRS parameters.

Methods: Real-time changes in cerebral concentration of oxy(HbO₂)-, deoxy(HHb)- and total haemoglobin (tHB μM) were measured at the bedside by NIRS (Hammamatsu; NIRO 300). Details of routine clinical observations/interventions were recorded.

Results: Four patients aged 18 – 23 years (median 18 years) with severe primary TBI were studied for 93 – 425 min (median 225 min). Changes in NIRS parameters in response to three events are shown below. Also, whole blood administration resulted in an increase in blood volume and oxygen extraction with increasing MAP and CPP.

Table

Conclusions: In this pilot study ‘routine’ clinical interventions/events such as ET suction, coughing and turning, lead to reproducible and reversible changes in blood volume and haemoglobin oxygenation. These observations indicate that NIRS is an extremely sensitive technique and hence results have to be interpreted with caution in the clinical setting.

A comparison of cerebral oximetry with angiographic changes during embolisation of intracranial anterior circulation aneurysms

R. Bhatia, S. Malde, M. Muammar, N. B. Kandala, N. Deasy, T. Hampton & A. J. Strong (Department of Clinical Neurosciences, King's College Hospital, London, UK)

Background: Near-infrared spectroscopy (NIRS) has been used to monitor regional cerebral oxygen saturation (rSO₂) in patients at risk of cerebral desaturation during surgical and neurointerventional procedures. However, the quantitative capabilities of the method have been questioned, as has its validation compared with jugular bulb oximetry.[1] Here, we compare NIRS data acquired during embolisation procedures with incidence of vasospasm detected during angiography.

Methods: Thirty-two SAH patients underwent embolisation. Bilateral SomaSensor strips (Invos 4100, Somanetics) were affixed to the forehead at constant anatomical positions, avoiding frontal sinuses and scalp hair. Mean arterial pressure, SaO₂, pCO₂, temperature and Hb were held within a narrow range during the procedure. Ipsilateral angiography was performed every 10 – 15 min. An independent neuroradiologist classified any vasospasm in the parent vessel as mild (25% baseline), moderate (50%), severe (75%) or total (100%).

Results: Fourteen out of thirty-two (43.8%) patients developed spasm; in two it was severe or total. There was no significant association between WFNS grade and baseline rSO₂ signal (ipsi/contralateral to the aneurysm side; p = 0.598. There was no significant association between side of aneurysm and baseline rSO₂ signal (p = 0.509). However, episodes of angiographic spasm were strongly associated with reduction in ipsilateral NIRS signal (p = 0.0001); furthermore, the degree of spasm (especially more than 75% vessel diameter reduction) was associated with a greater reduction in same-side NIRS signal (p = 0.0001). (Two-level, random effects multiple regression: Stata 8.2, Stata Corp, Texas, USA.)

Conclusions: NIRS may have a useful role to play in the detection of cerebral desaturation secondary to vasospasm during neuroendovascular procedures.

Study of cerebral circulation for patients with head injury

M. Honda¹, Y. Noguchi², T. Kushida³, S. Sase^2,5, K. Machida⁴ & Y. Seiki² (Departments of ¹Critical Care Center, ²Neurosurgery, ³Neurosurgery, and ⁴Radiology, Toho University Omori Medical Center, and ⁵Anzai Medical Co., Ltd., Tokyo, Japan)

Background: Severe traumatic brain injury (TBI) is widely known to cause a dynamic cerebral blood flow (CBF). Especially, decrease of cerebral blood flow (CBF) has been reported.

Methods: In the present study we measured the CBF, the mean transit time (MTT) and the cerebral blood volume (CBV). Our purpose was to investigate the possibility to predict the outcome with use of these physiological parameters, and the relationship between the clinical condition of the patients and these parameters. In 37 patients with TBI, Xe-CT and perfusion CT were performed at the same time in the phase II (days 1 – 3). We measured CBF by using Xe-CT and MTT by using perfusion CT and calculated CBV by using AZ-7000W98 computer system. We evaluated the relationship between these values and outcome, grading on admission and the presence of cerebral circulation disturbance.

Results: The results were correlated with the outcome and values of CBF and MTT. Significant differences in CBF and MTT were found between favourable outcome group (GR and MD) and poor outcome group (SD, VS and D). We could estimate the outcome of patients with TBI by analysing values of CBF and MTT. The probability was 74%.

Conclusions: These parameters can be helpful for the evaluation of cerebral circulatory disturbance and prediction of outcome for the patients with severe TBI.

Determination of extracerebral parameters affecting the near infrared spectroscopy (NIRS) indocyanine green (ICG) dye dilution method for cerebral blood flow measurement

R. Mudra¹, C. Muroi², B. Gaida², P. Niederer¹ & E. Keller² (¹Institute of Biomedical Engineering, and ²Neurointensive Care Unit, Department of Neurosurgery, University Hospital Zurich)

Background: The NIRS ICG dye dilution method[1] is used for monitoring of cerebral haemodynamics in neurointensive care patients. Early diagnosis of diminished cerebral perfusion is important to prepare optimal conditions for the brain to recover. The measurement quality is strongly dependent on the extracerebral component of the individual head, e.g. the skull thickness and measurement position.

Methods: In an approved study (Zurich Ethics Committee (No. E-36/2004)) in 10 healthy volunteers NIRS ICG dye dilution measurements are analysed to determine the extracerebral component. The optodes were fixated with a flexible headband over both hemispheres and optical density (OD) signals were monitored (sender detector distance 4.5 cm). ICG, 0.5 mg/kg BW was injected intravenously. In a rearranged composition of the optodes with one sender and two detectors spatial resolved spectroscopy (SRS) was performed and the extracerebral component within the OD signal determined. After both measurements, the optode positions have been marked. The healthy volunteers with the markers on the head were then CT scanned and skin, skull and cerebrospinal fluid (CSF) layer under the optode positions determined.

Results: The skin thickness under each optode position varies between 1.7 and 12.9 mm, while the skull thickness varies between 3.9 and 14 mm. The CSF volume under the optodes varies between 0.18 and 7.05 ml.

Conclusions: The OD signal quality is reduced, when either skull or skin thickness are high. Combined effects have to be further analysed.

Bilateral vertebral artery disease: transcranial Doppler assessment of the haemodynamic vulnerability to changes in posture

C. Haubrich¹, A. Kohnke¹, C. Kloetzsch², W. Moeller-Hartmann³ & R. R. Diehl⁴ (Departments of ¹Neurology, University Hospital Aachen, ²Kliniken Schmieder, Allensbach and Hegau-Klinikum Singen, ³Department of Neuroradiology, University Hospital Koeln, and ⁴Department of Neurology, Alfried-Krupp Krankenhaus Essen, Germany)

Background: Posture changes may cause haemodynamic ischaemic events, particularly in severe bilateral vertebrobasilar artery disease (BVAD). It may be difficult and not without risk to prove this vulnerability to changes in posture during angiography. Therefore, TCD monitoring with passive tilting (PT) was used to evaluate cerebral haemodynamics distally to severe BVAD.

Methods: Using continuous monitoring of beat-to-beat blood pressure and transcranial Doppler of the posterior cerebral arteries (PCA), the flow velocity responses to passive tilt and dynamic cerebral autoregulation (DCA) were analysed in 21 patients with BVAD and 22 controls. DCA testing was based on the ‘high-pass filter model’, which predicts a positive phase relationship between slow spontaneous oscillations of 3 – 9 cpm in arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV).

Results: Despite an autoregulatory deficit distally to BVAD with significantly diminished phase shift angles (11.4 ± 5.6°/15.0 ± 6.3°), the posterior cerebral blood supply seemed to be sufficiently maintained as long as systemic blood pressure changes were within normal limits. Posterior cerebral flow velocities, however, were significantly diminished (left to: 65.1 ± 11.5%; right to: 70.1 ± 2.9% of supine levels) when PT detected a systemic hypotension in up-right position.

Conclusions: Severe BVAD may lead to significant autoregulatory deficits of the posterior cerebral circulation in both supine and up-right positions. However, postural changes lead to a critically diminished posterior cerebral blood supply only under conditions of orthostatic hypotension. A combined examination of spontaneous and tilt-induced autoregulatory responses could support the evaluation of a risk for postural ischaemia in BVAD.

Tracing the dynamics of the cerebral autoregulation response to step-wise changes in PaCO₂

J. Liu, M. D. Simpson & R. Allen (Institute of Sound and Vibration Research, University of Southampton, Southampton, UK)

Background: Cerebral autoregulation has been studied by linear filter systems, with arterial blood pressure (ABP) as the input and cerebral blood flow velocity (CBFV, from transcranial Doppler Ultrasound) as the output. The current work extends this by using adaptive filters to investigate the dynamics of time-varying cerebral autoregulation during step-wise changes in arterial pCO₂.

Methods: Cerebral autoregulation was transiently impaired in 12 normal adult volunteers, by switching inspiratory air to CO₂/air mixture (5% CO₂, 30% O₂ and 65% N₂) for approximately 2 min and then back to the ambient air, causing step-wise changes in end-tidal CO₂ (EtCO₂). Simultaneously, ABP and CBFV were recorded continuously. Simulated data corresponding to the same protocol were also generated using an enhanced physiological model based on,[1] in order to refine the signal analysis methods. This consisted of adaptive filter modelling followed by the extraction of time-varying autoregulatory parameters (phase-lead, autoregulation index, ARI).

Results: The adaptive filter was able to follow rapid changes in autoregulation, as was confirmed in the simulated data. In the recorded signals, there was a slow decrease in autoregulatory function following the step-wise increase in pCO₂ (not reaching a steady state within approximately 2 min), with a more rapid change in autoregulation on return to normocapnoea.

Conclusion: Adaptive filter modelling can demonstrate time-varying autoregulation. Impairment and recovery of autoregulation during transient increases in EtCO₂ occur at differing rates.

Cerebral microvessel perfusion and pathologic alteration of the brain during drowsiness and coma, caused by brain tumour (a laboratory study in rats)

J. Hekmatpanah (University of Chicago Medical Center, Department of Surgery, Section of Neurosurgery, Chicago, USA)

Background: Deterioration of consciousness and coma, in cerebral compression, is traditionally thought to be caused by compression, shift, haemorrhage or herniation of the brainstem. This study was done to evaluate the vascular perfusion and pathologic alteration in the entire brain during drowsiness and coma.

Methods: Brain tumours were developed in three newborn rat litters by inoculation of Kirsten Sarcoma Virus (a murine erythroblastosis virus) in the brains. Within several weeks brain tumours developed. When animals became drowsy or comatose, their brains were perfused with microbarium, India ink or paraformaldehyde solution. In two animals, the brain vasculature was casted by plastic materials. Brains were fixed for magnification radiography or were prepared for histological examination.

Results: The brains of control animals showed an abundance of microvessels and penetrating capillaries, located perpendicular to the cortex and deep within the brain. The latter cannot be detected even in the best routine cerebral angiography in man. Microvessels were obstructed, in a patchy and dispersed fashion, in drowsiness especially in ipsilateral hemisphere. Obstruction of microvessels was present throughout the brain in animals in coma and larger vessels appeared markedly narrowed. The study also revealed evidence of diffuse infarcts, cellular ischaemia, swelling and periventricular damage throughout the brain.

Conclusion: During drowsiness and coma, caused by cerebral compression, cerebral capillaries progressively obstruct; during coma a large number of them are obstructed throughout the brain and cause dispersed microinfarcts. These likely causes diffuse neurological disabilities and behavioural changes often seen after recovery from coma caused by cerebral compression.

‘ICM + ’: versatile software for analysis of cerebrovascular dynamics in clinical practice

P. Smielewski^1,2, M. Czosnyka¹, P. Lewis¹ & J. D. Pickard^1,2 (¹Academic Department of Neurosurgery, and ²Wolfson Brain Imaging Centre, Addenbrooke's Hospital, Cambridge, UK)

Introduction: Contemporary brain monitoring in clinical practice includes multiple global and local modalities such as ABP, ICP, Transcranial Doppler, Laser Doppler Flowmetry, brain tissue oxygenation, jugular bulb oxygen saturation, near infrared spectroscopy, etc. Measured variables require time- and/or frequency-domain online analysis to derive further information from spontaneous waves present in those signals (e.g. cardiac-related, respiratory and slow waves). Analysis of cross-correlation between signals such as blood flow velocity, laser Doppler-flux or tissue oxygenation helps in the assessment of mechanisms related to cerebral blood flow regulation.

Methods: ICM + software has been developed in house, borrowing from our 10 years experience in data monitoring and analysis in the neurocritical care unit in Addenbrooke's Hospital, Cambridge. Previous versions of the software have allowed us to collect multimodal data from nearly 600 severely head-injured patients, along with secondary indices calculated online describing cerebral autoregulation and pressure-volume compensation. ICM + includes a calculation engine that allows easy configuration and real-time trending of complex parameters. The program records raw signals and calculates time trends of summary parameters. Configuration of analyses utilises arithmetic expressions of statistical and signal processing functions (moving average, correlation, power spectrum, coherence, etc.). The software allows configuration of several levels of analysis with the output of each one providing input to the next. The final data are displayed in a variety of ways including simple time trends, as well as time window based histograms, cross histograms, correlations, etc., to facilitate data browsing and mining. The postprocessing tools also support the calculation of indices of cerebrovascular reactivity from recordings made during interventions like transient hyperaemic response, rapid leg-cuff deflation and CO₂ reactivity tests. The ICM + package facilitates the modification of existing methods of analysis of cerebral haemodynamics and the development of new algorithms. In addition to on-line trends of calculated values and indices, the software also saves raw data from bedside monitors, which enables building up a library of signals for postprocessing. These saved raw signals can subsequently be processed using the on-line analysis engine, thus providing a means of testing novel indices and methods of on-line data processing. Tools for manual marking of, and automatic detection of artefacts in the input signals and resulting time trends are provided to ensure high quality of the analysis results.

Results: To verify the usefulness of ICM + for assessment of cerebrovascular dynamics, 187 patients with severe head injury were analysed. In total, 563 recordings of ICP, ABP and TCD FV from 187 patients were processed using a variety of different analysis configurations. Results showed strong correlations between autoregulation indices Mx, Prx and Outcome, and allowed detailed investigation of these relationships.

Conclusion: ICM + is a universal tool for clinical and academic purposes. Its flexibility and advanced signal processing features are specialised for the needs of multidisciplinary brain monitoring, and it is particularly well suited for investigations into cerebral haemodynamics.

Disclosure: ICM + software is licensed by University of Cambridge (see www.neurosurg.cam.ac.uk/icmplus). PS and MC have financial interest in a fraction of licensing fee.

Cerebral autoregulation after head injury

M. Czosnyka, P. Smielewski, P. Lewis & J. D. Pickard (Academic Neurosurgical Unit, University of Cambridge, UK)

Objective: The method for continuous assessment of cerebral autoregulation using time-domain correlation between slow waveform (20 – 120-s period) of MCA blood flow velocity and cerebral perfusion pressure (CPP) or arterial pressure (AP) has been introduced 10 years ago.[1] We intend to review clinical applications of this method in various scenarios following head injury.

Method: Moving correlation coefficient (3-min window), called Mx index, is calculated between low-pass filtered (0.05 Hz) signals of FV and CPP or AP.

Material: 293 ventilated head-injured patients hospitalised at Neurocritical Care Unit following head injury. TCD was recorded digitally along with ICP and AP daily within baseline periods (no interventions) from 20 min to 2 h.

Results: Mx correlated significantly with static rate of autoregulation. It showed good agreement with transient hyperaemic response test. Mx correlated strongly with pressure-reactivity calculated from changes between ICP and AP. Poor autoregulation proved to be an independent predictor of fatal outcome following head injury. It was significantly disturbed by intracranial hypertension (ICP > 25 mmHg). Autoregulation was worse for low CPP (CPP <55 Hg) and for too high CPP(>105 mmHg) than for normal CPP (between 60 and 100 mmHg). Asymmetry of cerebral autoregulation (left-right) was associated with asymmetry of CT scan- autoregulation was worse at the side of contusion and at the side of brain expansion causing midline shift. Asymmetry independently contributed to fatal outcome. Autoregulation after head injury worsens with age, probably contributing to worse outcome in elderly patients. Mx values calculated with CPP and AP are well correlated with each other (R = 0.85). However, association between outcome and CPP-based index is far stronger than between outcome and AP-based index. Mx showed deterioration of cerebral autoregulation in large (>4 µg/ml) plasma concentration of propofol, correlated with depletion of static rate of autoregulation.

Conclusion: Mx can be used in many clinical scenarios for continuous monitoring of cerebral autoregulation, predicting outcome and optimising therapeutic strategies.

Continuous cerebrovascular autoregulation: the link between CPP management and outcome

A. Girardini, A. Lavinio, I. Nodari, F. Rasulo & N. Latronico (Institute of Anaesthesia and Intensive Care, Spedali Civili University Hospital of Brescia, Italy)

Background: Autoregulation orientated cerebral perfusion pressure (CPP) management seems to be one of the most promising fields of research in modern neuro-critical care. Prospective studies were advocated since 2002 to verify the effectiveness of such a design. The purpose of the present paper is to evaluate the feasibility of an ‘optimal CPP’ orientated trial through assessment of optimal CPP ranges and to verify the prognostic impact of autoregulation on outcome.

Methods: Observational, retrospective study. Clinical setting: general, 12-bed ICU. Critically ill, comatose patients who underwent intracranial pressure (ICP) and invasive arterial blood pressure (ABP) monitoring on a clinical indication basis were enrolled. ICP and ABP were digitalised and computed by means of ICM + (Cambridge University Software, UK). Data were analysed offline after manual artefacts detection. Continuous cerebrovascular reactivity was assessed by means of the correlation coefficient ‘pressure reactivity index’ (PRx). 10-mmHg wide optimal CPP ranges (CPPopt, as previously defined by L. Steiner) were identified day by day. CPP was confronted to the CPPopt range on a minute per minute basis and classified as ‘below range’, ‘in range’ or ‘above range’. Mean PRx, duration of defective autoregulation crisis (PRx > 0.2) and outcome at ICU discharge (dead, alive) were evaluated.

Results: During the year 2005, a total of 30 patients had been monitored. They were admitted with a diagnosis of severe head trauma (n = 14), subarachnoid haemorrhage (n = 10), intracerebral haemorrhage (n = 4) and ischaemic stroke (n = 2). Mean age was 43.2 (SD 17.5) years, ranging from 17 to 78 years. The outcome at ICU discharge was seven dead and 23 alive. Mean monitoring time was 100.1 (SD 62.6) h per patient, ranging from 18 to 192 h, for a total monitoring time of 3102 h in 144 days. In 60 days (42%) a CPPopt range was identified while in 49 days (34%) a trend was recognised. In 35 days (24%) it was not possible to identify a CPPopt range or a trend. CPP was in the CPPopt range only in 26.3% of periods, below range in 37.1% and above range in 36.6% of periods. Patients who died had higher ICP (p = 0.006), worse mean PRx (p = 0.0002) and longer defective autoregulation crisis (p = 0.005). A non-statistically significant trend related better outcome to longer duration of periods where CPP was within the CPPopt range (p = 0.11) and, quite unexpectedly, to longer periods where CPP was above the CPPopt range (p = 0.015). Nevertheless, a CPP lower than CPPopt was a strong predictor of fatal outcome (p = 0.0019).

Conclusions: Within the limitations of a small and heterogeneous population, ICM + proved to be a very strong prognostic tool. Elevated PRx values and defective autoregulation crisis were strongly related to CPP lower than the CPPopt range and to fatal outcome. However, in our series and in contrast with previous literature, a CPP exceeding the CPPopt range was not related to worse outcome. Our first year experience suggests that a CPPopt orientated trial is feasible. We underline that a CPPopt orientated protocol may have changed CPP management in 73.7% of cases. In the meantime, since our data suggest that a CPP lower than CPPopt seems to configure an extremely risky situation, aggressive CPP treatment should promptly be instituted whenever CPP falls below the CPPopt range.

Optimising vascular to tissue oxygen gradients may overcome diffusion hypoxia in TBI

J. Nortje^1,3, J. P. Coles^1,3, I. Timofeev^2,3, T. D. Fryer³, F. I. Aigbirhio³, P. Smielewski^2,3, J. G. Outtrim^1,3, D. A. Chatfield^1,3, J. D. Pickard^2,3, P. J. Hutchinson^2,3, A. K. Gupta¹ & D. K. Menon^1,3 (¹University Division of Anaesthesia, ²Academic Neurosurgery Unit, and ³Wolfson Brain Imaging Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK)

Background: Cerebral ischaemia and hypoxia worsen outcome following traumatic brain injury (TBI). We used positron emission tomography (15O-PET) to examine whether hyperoxia (increased FiO₂) reverses cerebral hypoxia.

Methods: Following ethical approval and next-of-kin assent, TBI patients aged over 15 years, and requiring control of intracranial hypertension, were studied. Patients with coagulopathy, unstable physiology or requiring high FiO₂ (>0.5) were ineligible. Microdialysis, brain tissue oximetry (PbO₂), and 15O-PET was acquired at baseline and repeated after stabilisation at hyperoxia (FiO₂ 0.6 – 0.8). Non-parametric statistics were used.

Results: Eleven patients of mean (range) age 42 (17 – 64) were studied on median day 2 (1 – 9) postinjury. The median GCS was 5 (3 – 11). Two study failures were excluded before data analysis. Hyperoxia increased median (IQR) PbO₂ significantly [2.9 (2.2 – 3.4) v. 5.9 (4.1 – 7.0) kPa; p < 0.01]. Microdialysate lactate and pyruvate were unchanged, but the L/P ratio showed a small, but significant reduction [34 (28 – 42) v. 32 (26 – 38); p < 0.05]. 15O-PET oxygen extraction fraction (OEF) trended towards normality [0.31 (0.24 – 0.35) v. 0.31 (0.28 – 0.34), NS] with hyperoxia; revealing a reduction in high OEF and an increase in low OEF.

Conclusions: Reduction of high OEF may reflect correction of classical macrovascular ischaemia. Increases in low OEF, however, may be evidence of hyperoxia overcoming fixed diffusion barriers for oxygen delivery (microvascular ischaemia),[1] and correction of relative impairment in mitochondrial oxygen utilisation.[2]

Positron emission tomography for language localisation in children

M. Jalaluddin, A. M. Kaplan, M. A. Lawson & S. D. Moss (Department of Neurosurgery Phoenix Children's Hospital, University of Arizona & Department of Neurosciences, KFSH & RC, Saudi Arabia)

Background: The purpose of this study is to examine the role of [O15]water positron emission tomography(PET) to localise speech and language functions.

Methods: We have studied 30 children, 4 – 19 years age, with PET scans utilising [O15]water. Brain maps were acquired with activation of speech and language cortical functions.[1] These studies were performed in the preoperative evaluation of children with brain tumours and medically intractable seizures. All patients tolerated the procedure well. After intravenous administration of [O15]water, five baseline, five language and two motor speech activation studies were performed. The baseline data was subtracted from activation data and coregistered with the patient's magnetic resonance images (MRI) for subsequent viewing and interpretation. The cortical areas of language including expressive, receptive, motor speech and semantic components were analysed.

Results: [O15]water PET activation was able to localise language functions in 29 out of 30 (97%) patients; the expressive component in 29 (97%), receptive in 25 (84%), motor speech in 27 (90%) and semantic speech areas in 23 (77%).

Conclusions: [O15]water PET activation is a noninvasive and safe procedure for accurate localisation of language and speech functions.

Clinical use of quantitative measurement of cerebral haemodynamics with PET and MRI for juvenile patients with moyamoya disease

T. Nariai, Y. Tanaka, T. Momose, C. Hosoda, M. Aoyagi, K. Ishii, K. Ishiwata, Y. Matsushima & K. Ohno (Department of Neurosurgery, Tokyo Medical and Dental University, and Positron Medical Center, Tokyo Metropolitan Institute of Gerontology Tokyo Japan)

Introduction: To construct the optimum treatment strategy for patients with moyamoya disease, getting information on haemodynamic condition of each patient[1] is necessary. We reported our experience in treating juvenile patients with moyamoya disease using the reliable haemodynamic measurement.

Methods: We measured the haemodynamics of 60 juvenile patients with moyamoya disease (mean 9.3 years old, 1 – 19) preoperatively using perfusion weighted MRI (60 patients)[2] and/or PET (22 patients). Treatment strategy was determined based on the result of these studies.

Result: (1) Using the data of PWI or PET, surgical indication and the procedure were determined and 62 operations to 100 hemispheres of 55 patents were performed. (2) All were treated with combined use of various indirect bypass procedures depending on the site and the severity of haemodynamic compromise. (3) Among all operated cases new infarcted lesions were detected in five hemispheres of four patients and two were symptomatic. In all others, no new infarction detected and amelioration of TIA together with haemodynamic condition was achieved.

Conclusion: Precise measurement of haemodynamic condition was possible even in juvenile patients using MRI or PET. Indirect bypass surgery in combination with haemodynamic measurement was highly effective strategy to control ischaemic symptom of juvenile patients with moyamoya disease.

The role of haemodynamics in intracranial aneurysm formation: a computational fluid dynamics model

S. Howarth¹, Z-Y. Li¹, T. Tang¹, P. J. Kirkpatrick² & J. H. Gillard¹ (¹University Department of Radiology, and ²Academic Department of Neurosurgery, Addenbrooke's Hospital, Cambridge, UK)

Background: Rupture of intracranial aneurysms is a common cause of spontaneous subarachnoid haemorrhage and results in significant morbidity and mortality. Haemodynamics is often thought to play an important role in predisposing aneurysms to rupture; however, descriptors that can describe aneurysm formation are not well understood. We examined the fluid dynamics within various cerebral artery bifurcation models with different open angles to define factors that may be helpful in predicting aneurysmal formation.

Methods: An idealised cerebral artery bifurcation model was used and a computational fluid dynamics approach was used to determine the velocity field, wall shear stress, and pressure distribution within this model. The flow was modelled as Newtonian flow and an incompressible Navier-Stokes equation was used for the numerical simulation. The open angle of the bifurcation was varied from 200 to 900, and the arterial wall stress and flow condition were examined.

Results: Large recirculation zones were predicted at the bifurcation when the open angle was large. Distribution of wall shear stress was not uniform in the arterial walls. There was a high shear stress gradient and large pressure increase at the bifurcation. The arterial wall stress was increased by 57% when the open angle of the bifurcation was varied from 200 to 900.

Conclusion: Our results from non-linear finite element analysis reveal an important role of vessel bifurcation angle in governing the distributions of shear stress within the aneurysm dome. The next step is the use of this model on patient data sets of individuals treated expectantly to assess if increased arterial wall stress correlates with rate and direction of aneurysm growth.

Ratio between changes in cerebral blood volume and flow depends on vascular reactivity content in a voxel—a modelling study

S. K. Piechnik, P. Chiarelli & P. Jezzard (University of Oxford, Centre for Functional Magnetic Resonance Imaging of the Brain, John Radcliffe Hospital, Oxford, UK)

Introduction: We aim to better understand the relationship between relative changes in cerebrovascular volume and flow [v(f)] with the help of three models of cerebral circulation: M1 – 3.

Methods: M1 is a uniform reactive tube. Three-compartmental M2 contains additional constant resistive inflow and voluminous outflow (α, β of total resistance and volume at rest). M3 is a multilevel hierarchical network with distributed reactivity dependent on vessel-size, type and CO₂ level. The reactivity function was obtained by fitting data from experimental studies using direct measurement of diameter.

Results: The model choice changes the v(f) shape from a simple power function fitted by Grubb (v = f ∧ 0.38),[1] which itself was designed as a scaled version of M1 (v = f ∧ 0.5). However, within the experimentally relevant range of changes (f = 0.7 – 1.60) the relation closely approaches linear which can be described just by a slope k, roughly equivalent to the Grubbs exponent. K depends strongly on the ratio of regulating to non-regulating vessels in the volume of interest. In M3, the microvascular compartment has the steepest (k = 1.09), the venous compartments the flattest v(f) curve (k ∼ 0.06).

Conclusions: The non-linearity of v(f) relationship lies within the experimental measurement error. The overall trend to increase the slope with the content of regulating vessels is in agreement with a recent PET study demonstrating highest coupling in white matter, which is predominantly devoid of large vessels.[2] Such systematic variability of v(f) coupling confounds the interpretation of focal metabolic findings from high resolution imaging such as MRI where measurements of flow and volume may be weighted towards different cerebrovascular compartments.

Fibrous cap thickness is critical to atheromatous plaque rupture: a pulsatile flow-plaque interaction model

Z-Y. Li¹, S. Howarth¹, T. Tang¹, P. J. Kirkpatrick² & J. H. Gillard¹ (¹University Department of Radiology, and ²Academic Department of Neurosurgery, Addenbrooke's Hospital, Cambridge, UK)

Introduction: Rupture of vulnerable carotid atheroma is a common cause of cerebral ischaemic events as a result of distal embolisation affecting cerebral haemodynamics. Selection of patients for intervention is currently based on the severity of carotid luminal stenosis, although evidence is growing that luminal stenosis alone may not be an adequate predictor of risk and factors such as fibrous cap thickness and biomechanical stress are thought to also play major roles. To evaluate the effects of degree of luminal stenosis and fibrous cap thickness on plaque stability, we set up a flow-structure interaction model and simulated the interaction between blood flow and atheromatous plaque in an idealised model of the carotid artery.

Method: A coupled non-linear time-dependent model with flow-plaque interaction simulation was used to perform flow and stress/strain analysis for the stenotic artery and an associated plaque. The Ogden strain energy function was used for both the fibrous cap and the lipid pool. The plaque principal stresses were calculated for every case when varying the fibrous cap thickness from 0.1 mm to 3 mm and the degree of luminal stenosis from 10 to 95%.

Results: Severe stenosis led to high flow velocities and high shear stresses, but a low or even negative pressure at the throat of the stenosis. Higher degree of stenosis and thinner fibrous cap led to larger plaque stresses, and a 50% decrease of fibrous cap thickness resulted in a 40% increase of maximum stress.

Conclusions: This model suggests that fibrous cap thickness is critically related to plaque vulnerability and that, even within presence of moderate stenosis, may play an important role in the future risk stratification of those patients when identified in vivo using high resolution MR imaging.

Effect of L-arginine on CBF in TBI patients with regional or global ischaemia

R. Hlatky, J. C. Goodman, A. B. Valadka & C. S. Robertson (Department of Neurosurgery, University of Texas, San Antonio, and Department of Neurosurgery, Baylor College of Medicine, Houston, USA)

Occurrence of ischaemia following TBI correlates with adverse outcome. L-arginine (L-Arg), the substrate for nitric oxide synthase, restores CBF near to pre-injury levels, and reduces the extent of TBI in experimental studies. The purpose of the study was to examine the effect of L-Arg on CBF in TBI patients with regional or global ischaemia (CBF < 20 ml/100 g/min).

Nine patients were randomly assigned to receive or L-Arg (single dose, 300 mg/kg BW) or normal saline. Effects on global and regional CBF using XeCT were investigated. The study was terminated early (75 patients proposed) because Xe became unavailable for measuring CBF in the US.

The primary outcome measure was the global CBF. Global CBF tended to be lower during baseline in L-Arg patients (25.8 + 6.7 v. 30.6 + 9.8 ml/100 g/min), but increased a similar amount with both treatments (10.4 + 6.7 v. 15.1 + 10.8 ml/100 g/min). When the proportion of the total cortical CBF with values less than 20 ml/100 g/min was assessed, similar results were obtained. The percentage of the brain below the ischaemic threshold was higher at baseline in the L-Arg treated group (49.9 + 27.4% compared with 38.1 + 13.8%), and this percentage decreased with treatment in both groups. The amount of decrease was similar in both groups (L-Arg −24.1 + 13.1%; normal saline −25.3 + 13.2%).

The numbers of patients are too small to draw any definitive conclusions, but it appears that there is no clear effect of L-Arg on global CBF in these very severely injured patients. One explanation could be severity of the injury (inclusion criterion - regional or global ischaemia defined by CBF < 20 ml/100 g/min), another possible explanation could be individual variability in the ability to respond to L-Arg administration.

Evaluation of brain-blood partition coefficient for xenon in patients with subarachnoid haemorrhage

S. Sase^1,2, M. Honda³, T. Kushida⁴, Y. Noguchi², K. Machida⁵ & Y. Seiki² (¹Anzai Medical Co., Ltd., Departments of ²Neurosurgery, Critical Care Center,³ and ⁵Radiology, Toho University Omori Medical Center, Tokyo, and ⁴Department of Neurosurgery, Toho University Sakura Medical Center, Chiba, Japan)

Background: Brain-blood partition coefficient (lambda) for xenon and CBF were evaluated to know their time course changes in the early stage after the onset of aneurismal subarachnoid haemorrhage (SAH).

Methods: Twelve patients with aneurismal SAH were studied (56.4 ± 8.4 years). For each patient, the first and second Xe-CT examinations were performed in the pre-spasm stage (2 – 5 days after the onset) and several days later. CBF and modified lambda (mλ) maps were created; an mλ map is composed of pixels whose λ values do not exceed unity. Six regions were specified according to the right and left territories of the ACA, MCA and PCA. For each region, CBF and λ values were measured using the CBF and m λ maps, respectively. We selected the 12 patients on condition that each region's CBF was more than 20 ml/100 g/min in the first Xe-CT examination. For each patient, we calculated the CBF ratio (second CBF/first CBF) and λ ratio (second λ/first λ) for each region, and determined the average CBF and λ ratios for the six regions.

Results: Significant correlation was found between the average λ ratio and the Glasgow Outcome Scale (GOS) score (r = 0.695, p = 0.0101), and between the average CBF ratio and the GOS score (r = 0.616, p = 0.0312).

Conclusions: It was suggested that time course changes in λ and CBF in the early stage after the onset of SAH could reflect the clinical outcome. It would be informative to examine both of λ and CBF in following up SAH patients.

The measurement and evaluation of CBF, CBV and MTT on patients with severe subarachnoid haemorrhage during therapeutic hypothermia using Xe-CT and perfusion CT

T. Kushida¹, M. Honda², S. Sase³, T. Nagao¹, N. Sugo⁴ & Y. Seiki⁴ (¹Department of Neurosurgery, Toho University Sakura Medical Center, Chiba, ²Critical Care Center and ⁴Department of Neurosurgery, Toho University Omori Medical Center, and ³Anzai Medical Corporation, Tokyo, Japan)

Background: We evaluated cerebral circulation during therapeutic hypothermia for patients with severe subarachnoid haemorrhage (SAH).

Methods: Thirty-seven subjects were examined by Xe-CT and perfusion CT: 10 patients with severe SAH (G.C.S: 8 or less) under moderate hypothermia (Group A), 17 patients with severe SAH sedated with propofol (Group B) and 10 normal volunteers (Group C). Ten regions of interest (ROIs) were placed: both hemispheres, right and left thalamus and territories of right and left main trunks of the cerebral arteries (Anterior cerebral arteries (ACA), middle cerebral arteries (MCA), posterior cerebral arteries (PCA)). For each ROI, we measured CBF by Xe-CT and mean transit time (MTT) by perfusion CT, and calculated cerebral blood volume (CBV).[1] Statistical comparisons for CBF, CBV and MTT were performed between Group A and B and between Group A and C by Mann-Whitney analysis.

Results: The average CBF values for the territories of ACA (a) and thalamus (t) were significantly low in Group A [15.4(a) and 24.2(t) ml/100 g/min, p < 0.001] than those in Group B [31.2(a) and 59.0(t) ml/100 g/min] and Group C [42.0(a) and 60.8(t) ml/100 g/min]. The average CBV values for the ACA territories and thalamus were significantly low in Group A [1.97(a) and 3.87(t) ml/100 g] than those in Group B [3.87(a) and 5.67(t) ml/100 g] and Group C [6.17(a) and 8.98(t) ml/100 g]. No significant difference was found in MTT between these three groups.

Conclusions: We speculated that CBV reduction by hypothermia therapy has an important role on protection against severe brain damage in case of SAH.

Alpha-stat versus pH-stat guided ventilation in patients with large ischaemic stroke

R. Kollmar^1,3, D. Georgiadis¹, W. Mier², J. Hoffend², J. Bardutzky¹ & S. Schwab³ (Departments of ¹Neurology, and ²Nuclear Medicine, University of Heidelberg, and ³Department of Neurology, University of Erlangen, Germany)

Background: Moderate hypothermia (MH) is a new therapeutic approach for ischaemic stroke as well as cardiac arrest. However, different modes of ventilation under MH influence cerebral blood flow (CBF) and thus intracranial pressure (ICP) by alteration of the acid-base status. We therefore investigated the effects of alpha- and pH-stat ventilation in patients with large ischaemic stroke treated with MH.

Methods: Eight patients with large ischaemic stroke in the territory of the middle cerebral artery (MCA) were treated with MH (33°C) within 24 h of symptom onset for 72 h. ICP, CBF, and mean arterial blood pressure (MAP) were measured. The xenon clearance method was used to assess CBF at the bedside. Each day, patients were ventilated repetitively with either alpha-stat or pH-stat for 60-min periods while under MH.

Results: There were no significant differences between ICP values for alpha-stat or pH-stat during days 1 and 2 after induction of hypothermia. However, ICP was higher in the pH- as compared with the alpha-stat group (p < 0.05) and exceeded a mean of 20 mmHg on day 3. PH-stat led to a significant increase of CBF in all measures (p < 0.05), while MAP was unaffected.

Conclusions: PH-stat guided ventilation may be indicated for the early phase of hypothermia in patients with large ischaemic stroke as it leads to an increase of CBF. However, after 48 h pH-stat can cause an undesirable increase of ICP.

Transdermal glyceryl trinitrate maintains cerebral blood flow and perfusion pressure whilst lowering blood pressure in patients with acute stroke

P. M. W. Bath¹, M. Willmot¹ & J. Wardlaw² (¹Institute of Neuroscience, University of Nottingham, and ²Division of Clinical Neurosciences, University of Edinburgh, UK)

Background: High blood pressure (BP) is common in acute stroke and independently associated with a poor outcome. Lowering BP might improve outcome if it did not adversely affect cerebral blood flow (CBF) or cerebral perfusion pressure. We investigated the effect of glyceryl trinitrate (GTN, a nitric oxide donor) on quantitative CBF, BP and cerebral perfusion pressure in patients with recent stroke.

Methods: Eighteen patients with recent (<5 days) ischaemic (n = 16) or haemorrhagic (n = 2) stroke were randomised (2:1) to transdermal GTN (5 mg) or control. CBF (global, hemispheric, arterial territory, lesion, using xenon CT) and BP (peripheral and central) were measured before and 1 hour after treatment with GTN. The effect of GTN on CBF and BP were adjusted for baseline measurements (ANCOVA).

Results: GTN lowered peripheral systolic BP by (mean) 23 mmHg (95% confidence intervals 2, 45, p = 0.03), and central systolic BP by 22 mmHg (95% CI 0, 44, p = 0.048). In contrast, GTN did not alter CBF (ml/min/100 g): global −1.2 (95% CI −6.5, + 4.2, p = 0.66), ipsilateral hemisphere −1.4 (−7.6, + 4.9, p = 0.65); or area of stroke oligaemia, penumbra or core (as defined by critical CBF limits). Contralateral CBF did not change: hemisphere 0 (95% CI −7, + 6, p = 0.96). GTN did not alter cerebral perfusion pressure or zero filling pressure.

Conclusions: Significant reductions in BP following transdermal GTN are not associated with changes in CBF or cerebral perfusion pressure, or cerebral steal in patients with recent stroke. Trials need to assess the effect of lowering BP on functional outcome.

What is wrong with dynamic cerebral autoregulation measurement?

R. B. Panerai (Department of Cardiovascular Sciences, University of Leicester, Medical Physics Group, Leicester Royal Infirmary, Leicester, UK)

Most studies of dynamic cerebral autoregulation (CA) have used transcranial Doppler to assess the swiftness of the cerebral blood flow velocity (CBFV) return to its baseline value following sudden changes in arterial blood pressure (ABP). Many different techniques have been applied to thousands of patients to demonstrate that dynamic CA indices are sensitive to deterioration of CA in severe head injury, carotid artery disease, stroke and other conditions.[1] Nevertheless, no single method has been accepted as a standard and most methods have shown considerable variability and poor reliability when applied to individual patients. ABP changes can be induced with special manoeuvres or obtained from spontaneous fluctuations. Both approaches have advantages and limitations. Quantification and modelling of the CBFV response has been performed both in the time- and frequency-domain, mainly by linear methods, despite the obvious non-linearity of CA mechanisms. Recently it has been shown that a multivariate linear model can overcome the main non-linearity due to changes in cerebrovascular resistance.[2] Most models have ignored the temporal variability of dynamic CA indices and the influence of co-variates such as the degree of mental activation during measurements. The influence of other determinants of CBFV, such as ICP, sympathetic activity and cerebral venous pressure, on indices of CA also needs to be further investigated. More studies on inter-method comparisons are important to assess their degree of agreement and advance towards more rigorous standards for dynamic CA measurement.

Dynamic cerebral autoregulation is altered in obstructive sleep apnoea syndrome

N. Nasr, A. Pavy-Le Traon, M. Czosnyka¹, M. Tiberge, E. Schmidt & V. Larrue (Neurosonology Unit, Neurology Department. Rangueil Hospital. Toulouse. France, and ¹Department of Neurosurgery, Addenbrooke's Hospital, UK)

Background: Obstructive sleep apnoea syndrome (OSAS) is an independent risk factor for ischaemic stroke.[1] Impairment of cerebral autoregulation may play a potential role in the predisposition to stroke of OSAS patients. We aimed in this study to assess dynamic cerebral autoregulation (DCA) in OSAS patients compared with controls.

Methods: Patients and controls were explored after an overnight complete polysomnography. Main exclusion criteria were a history of cerebrovascular disease, intracranial arterial stenosis and carotid stenosis as detected by duplex ultrasonography. Mean cerebral blood flow velocity (CBFV) in the middle cerebral artery and mean arterial blood pressure (ABP) were continuously recorded using transcranial Doppler and Finapres. Correlations between ABP and CBFV spontaneous fluctuations were averaged to form the correlation coefficient Mx.[2]

Results: All examinations were performed in the morning, within 2 – 3 h after awakening. Eleven OSAS patients (mean age ± SD; 52.6 ± 7.9) and nine controls (mean age ± SD; 49.1 ± 5.3) were enrolled. The mean apnoea-hypopnoea index (AHI) in the OSAS group was 22.7. No significant difference was found between the two groups as for age, body mass index, mean ABP and end-tidal CO2 pressure. Mx was significantly higher in OSAS patients compared with controls (0.414 v. 0.233; p = 0.009). Furthermore, Mx was positively correlated to the severity of the sleep respiratory disturbance as defined by the AHI (p = 0.003).

Conclusions: DCA is altered in OSAS patients. This finding may contribute to the understanding of the increased risk of stroke in OSAS.

Cerebrovascular reserve capacity after ECIC bypass surgery: TCD study

M. Sames, R. Bartos, P. Vachata, F. Cihlar & A. Hejcl (Masaryk Hospital, Usti nad Labem, Czech Republic)

Cerebrovascular reserve capacity is an elementary indication criterion for extra-intracranial bypass surgery. Transcranial Doppler (TCD) is a screening examination, which in our algorithm is followed by SPECT, perfusion CT or MRI.

We examined 12 ‘haemodynamically healthy’ volunteers in 2005 in order to set the referential values of our laboratory (six males, six females, average age 47 years, ICA stenosis excluded with ultrasound, no history of CVA, smokers/non-smokers 7:5). We used the modified Ringelstein's method of quantification (VMR, Stroke 1988). Vasomotor reactivity tests were performed using inhalation of 7.5% mixture of CO₂ and a breath hold test (BHT). We measured V_mean in MCA bilaterally, PI (Gosling), VMR CO₂, VMR BHT a TTP (time to peak, the time from the beginning of the vasomotor reactivity test until reaching the maximum velocity).

• Average relative increase of the V_mean/N-BH/ in our study during the BHT was 48% (SD 29).

• Average relative increase of the V_mean/N-CO₂/ in our study during CO₂ inhalation was 75% (SD 24).

• TTP is a variable parameter (max. 2.5 min).

In the second part of the study we compare the ‘physiological’ values of the CVR capacity using the same technique with the CVR capacity of 11 patients who underwent the ECIC bypass surgery, with a minimum interval of 3 months after the surgery. In all patients the CVR capacity was significantly reduced, exhausted or we observed the steal phenomenon before surgery. The group comprises those patients who were operated at the Masaryk Hospital in Usti nad Labem, Czech Republic in 2005. The patients are divided into groups according to the early angiographic control of the bypass (modified according to Schmiedek, 1994): grade 1 (two patients), grade 2 (two patients), grade 3 (five patients) and grade 4 – retrograde filling of the ACA (two patients).

The goal of the study is to assess the restitution of the CVR capacity based on the angiographic evaluation of the bypass function.

Are Doppler waveform contours indicators of cerebrovascular tone?

S. M. Byrd, A. Hughes, S. A. Thom & K. H. Parker (NHLI, International Centre for Circulatory Health, Imperial College, London, UK)

Background: The contours of Doppler waveforms and the underlying physiology, which creates them, have been a subject of interest since the inception of Doppler ultrasound for arterial assessment. We used vasomotor reactivity testing[1] to produce cerebral vasodilatation and vasoconstriction, and then analysed waveform shape changes during these changes in vascular tone.

Methods: The left middle cerebral artery Doppler velocity signal from 10 healthy subjects, mean age 32 years (22 – 51 years, six male) was obtained via a specially designed TCD data acquisition and analysis system. A single ensemble-averaged waveform was generated from 16 s of continuously recorded data from each subject. We then measured 12 different parameters of the waveform contour (local extrema, timing, rates of acceleration/deceleration) to define its characteristics. Subjects underwent vasomotor reactivity testing (CO₂ inhalation and hyperventilation), and waveform contour analysis. Data are presented in medians (inter-quartile range).

Results: There were distinct alterations of wave shape during mid-systole (peak velocity to aortic valve closure) when the regulating vessels influenced the wave contours, producing either a sharp increase in velocity deceleration (linked to vasoconstriction), or a short period of reduced deceleration followed by a velocity plateau and/or rise (linked to vasodilatation). The largest change occurred in the rate of deceleration after peak velocity, when the deceleration was slowed by a third (−33%, −100, −25) during CO₂ inhalation, but increased +70% (+56, +135) during hyperventilation (p = 0.01). All other waveform parameter changes during vasoreactivity were small (range 3 – 48%); median blood pressure change was 5.4% (2.5, 8.3) and heart rate was 20% (14.2, 21.0).

Conclusions: Doppler waveform contours in mid-systole appear to be linked with changes in vascular tone, and may prove to be sensitive indicators. In the future, this may be a clinically useful tool in neuro-intensive care.

Cerebral vasoreactivity assessment in patients with carotid stenosis: a comparison of infraclinoid internal carotid artery to distal middle cerebral artery

S. C. P. Ng, M. T. V. Chan & W. S. Poon (Division of Neurosurgery, Departments of Surgery, and Anaesthesia and Intensive Care, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong)

Background: Assessment of cerebral vasoreactivity (CVR) to carbon dioxide (CO₂) is a helpful tool for identifying patients with stenosis or occlusion of the internal carotid artery (ICA), who are at higher risk for haemodynamic strokes. The aim of this prospective observational study is to assess the utility of blood flow velocity (BFV) measurement by transcranial Doppler ultrasonography (TCD) at the ICA siphon compared with that at the usual middle cerebral artery (MCA) for the assessment of CVR to CO₂ in patients with carotid stenosis.

Methods: Seventy-five patients aged 18 years with carotid stenosis confirmed by imaging were included. BFV in both MCA and ICA were measured and monitored continuously by TCD before and after CO₂ administration. The percentage change in BFV per unit change in end-tidal CO₂ quantified CVR.

Results: In 35 out of 150 hemispheres (20 patients), CVR at MCA could not be determined unilaterally or bilaterally due to inadequate temporal window whereas CVR at ICA could be determined in all patients. Pearson correlation (R) of the two ratios was 0.442 (p < 0.0005). Compared with the thresholds of CVR at MCA, the accuracy of using CVR at ICA siphon in determining preserved and impaired CVR was fair (areas under the receiver operating characteristic curves >0.73). A trend toward a difference (p = 0.060) in CVR at ICA siphon was found between patients with symptomatic (n = 48) and asymptomatic stenosis (n = 27). Correlation between two CVR ratios in symptomatic was improved (R = 0.604, p < 0.0005), but not significant in asymptomatic patients (R = 0.174, p = 0.297). Further analysis of the cerebral blood flow (CBF) at MCA territories, measured by xenon enhanced computer tomography (XeCT) in 25 patients, a trend toward CBF asymmetry was found in symptomatic (n = 18, p = 0.062), but absent in asymptomatic (n = 7, p = 0.520) patients.

Conclusions: BFV measurement at ICA siphon can be a useful alternative in determining CVR to CO₂, especially in patients with symptomatic carotid stenosis. The association between the two CVR ratios may indicate the efficacy of collateral flow in symptomatic and asymptomatic patients. Further confirmation with angiographic and CBF findings are indicated.

Effects of acute treatment with pravastatin on cerebral autoregulation in patients after aneurysmal subarachnoid haemorrhage

M. Y. Tseng, M. Czosnyka, H. Richards, J. D. Pickard & P. J. Kirkpatrick (Department of Neurosurgery, Addenbrooke's Hospital, University of Cambridge, Cambridge, Cambridgeshire, UK)

Background: We have demonstrated that acute treatment with pravastatin following aneurysmal subarachnoid haemorrhage (aSAH) can ameliorate vasospasm and reduce delayed ischaemic deficits (DID).[1] Here, we assess the hypothesis that the effects are associated with an improvement in cerebral autoregulation.

Methods: Eighty aSAH patients (age 18 – 84 years, onset 1.8 ± 1.3 days) were randomised equally to receive either oral pravastatin 40mg or placebo for up to 14 days. Autoregulation was measured using daily transient hyperaemic response (THR) test and pressure reactivity index (PRx). The PRx is derived from mean arterial pressure and intracranial pressure (ICP) measured by ICP monitoring or external ventricular drainage from day 0 to 5. Data was compared between trial groups, and between patients with/without vasospasm, DID, or unfavourable outcome.

Results: Initially, on day 0 there was no difference in the autoregulation indices between groups. Thereafter the pravastatin group had shorter durations of impaired autoregulation, and a higher THR ratio. A significant correlation occurred between PRx and the ipsilateral THR ratio (r = −0.635, p = 0.008). However, no correlation was found between the PRx, statin treatment, vasospasm, DID, and outcome. Patients with vasospasm, severe vasospasm, or DID had significantly longer durations of autoregulation dysfunction and lower THRR values when compared with those without complications.

Conclusions: The neuroprotective effect of statins therapy following aSAH was associated with preserved cerebral autoregulation. A routine and daily assessment using THR test may help identify patients associated with higher risk of secondary insults.

A case of negative critical closing pressure

P. Gazzoli, M. Frigerio, E. De Peri, F. Rasulo, R. Gasparotti, A. Lavinio & N. Latronico (Institute of Anaesthesia and Intensive Care, Spedali Civili University Hospital of Brescia, Italy, Institute of Neuroradiology, Spedali Civili University Hospital of Brescia, Italy)

Background: Critical closing pressure (CCP), which is defined as the minimum transmural pressure under which cerebral blood flow (CBF) arrests and the vessel collapses, has recently been proposed as the real determent of cerebral perfusion.[1] Recent progress has been made in quantifying CBF and blood volume (CBV) through use of perfusion brain CT.

Case report: A 40-year-old female patient admitted to our ICU for massive SAH and hydrocephalus following a ruptured aneurysm of the right vertebral artery. Initial transcranial Doppler (TCD) showed low flow velocity and high pulsatility index in both middle cerebral arteries signifying low cerebral blood flow. The aneurysm was embolised and an EVD inserted. A trans-hyperaemic-response test (THRT) was performed and showed loss of cerebral autoregulation after which a gradual rise in ICP (40 mmHg) was observed. Brain CT showed increase in brain oedema and the decision to perform decompressive craniectomy was undertaken. The following day ICP was 20 mmHg and TCD exam showed high flow velocities and a Lindegaard ratio <3, signifying hyperaemia. The estimated CCP (Weyland method), resulted to be negative (−0.47 mmHg on the right and −5.49 mmHg on the left). A perfusion brain CT was performed which showed CBF and CBV values also compatible with cerebral hyperaemia: left = CBF 79.77 (±14.66) e CBV 13.56 (±2.04); right = CBF 77.95 (±18.16) e CBV 13.61 (±2.44). The days that followed were characterised by an increase in brain oedema and refractory ICP followed by a gradual worsening of the patient's clinical condition leading eventually to death.

Conclusions: In the patient observed, the presence of vasoplegia and disautoregulation led to hyperaemia, increase in CBV and refractory ICP. This was also confirmed by the values obtained by perfusion brain CT and documented by the negative CCP readings. Measuring CCP may be a useful adjunct to brain imaging techniques such as perfusion brain CT when diagnosing alterations in brain haemodynamics.

State of the ophthalmic collateralisation after ECIC bypass

R. Bartos, P. Vachata, M. Sames & A. Hejcl (Masaryk Hospital, Usti nad Labem, Czech Republic)

Extracranial ICA occlusion associated with CVR capacity exhaustion due to insufficient collaterals is associated with 8% risk of haemodynamic CVA. Ophthalmic perfusion is in cases of ICA occlusion the 3rd most important collateral; it can be realised via the supraorbital, supratrochlear, facial or maxillar artery. We indicate the ECIC bypass in patients with symptomatic ICA occlusion after excluding contralateral significant ICA stenosis, territorial infarction on brain CT and, in cases of exhausted CVR, capacity of the MCA (assessed by SPECT and TCD). New methods in our examination algorithm include perfusion CT and MRI. Stress examination during TCD assessment is realised using inhalation of 7.5% of CO₂. Now we concentrate on assessment of the collateral flow via the ophthalmic artery. Using compression tests, we assess its potential dependency on the frontal branch of the temporal superficial artery, a potential donor. Two basic types of bypass can thus be performed: 1. frontal branch can be ligated or used as a donor 2. the frontal branch must be saved as a collateral with a possible need to use an intergraft (radial artery). In the years 2001 – 2003 we performed 19 ECIC bypasses, in eight of them the cranialised frontal branch of the temporal superficial artery was preserved. Now we evaluate the long-term state of the collateral flow. In all patients, the cranialisation of the bypass is excellent, in six patients the CVR capacity was restituted on the MCA. In only one patient we observed spontaneous extinction of the ophthalmic collateral. Preservation of the ophthalmic collateral during ECIC bypass surgery is rational, simple and does not worsen the function of the bypass.

An analysis of micro- and macro-vasculature effects during graded stimulation

Y-C. L. Ho, E. T. Petersen, I. Zimine & X. Golay (Department of Neuroradiology, National Neuroscience Institute, Singapore)

Background: Traditional single-compartment, single time-point MRI arterial spin labelling methods assume unchanging arrival times (ATs) for CBF estimation. Using a recently developed MRI method,[1] we investigated CBF, arterial blood volume (aBV) and changes in arterial and microvascular ATs upon graded visual stimulation.

Methods: Six healthy subjects were presented with 25, 50 and 100% checkerboard contrasts and scanned twice using the QUASAR sequence,[1] with and without crusher gradients: α = 27°, TR/TE1 = 3000/23 ms, ΔTI = 100 ms, time points = 26, SENSE = 3, crusher encoding velocity Venc =[∞,3 cm/s]. Arterial input functions (AIFs), arterial blood volumes (aBV), arterial (τa) and microvasulature (τm) ATs were calculated according to Petersen et al.[1]

Results: With rising stimulation, CBF and aBV increased from baseline while τa, τm and τm-a decreased (table below). Despite significantly changing ATs, the CBF changes of up to 30% are relatively muted. The aBV increase with increasing stimulation was interesting, as it was not expected of larger vessels (>200 μm).

Table

Conclusions: Our results show that functional CBF quantification should not assume unchanging ATs. A capillary washout effect could be proposed to explain the intriguing relationship of increased blood velocities (shorter transit times) and relatively muted CBF changes.

Low-radiation-dose perfusion CT 1: attempt of dose reduction of radiation exposure for patients

H. Itokawa, R. Suzuki, M. Okuda, M. Moriya, A. Matsunaga, G. Nagashima & T. Fujimoto (Department of Neurosurgery, Fujigaoka Hospital, Showa University, Yokohama, Japan)

Background: The aim of this study was to evaluate perfusion CT protocols to determine how best to minimise patient exposure to ionising radiation while maintaining sufficient image quality.

Methods: In the basic study, continuous data acquisition was performed with the following technical parameters: 40-s acquisition time, 1-second rotation time, 10-mm section thickness, 80 kV tube voltage and 200 mA tube current. Image quality was evaluated by the noise level of CT scans in the acrylic phantom at various tube current (10 – 100 mA) and fixed three tube voltages of 80, 120 and 140 kV. The computed tomography dose index (CTDI) was determined by scanning an acrylic phantom at routine protocol and low-radiation-dose protocols (low-CTP) that were almost the same noise level with routine protocol. Image quality and cerebral perfusion parameters of low-CTP were compared with the results obtained with routine protocol.

Results: Low-CTP can reduce the CTDI by 70% compared with the CTDI derived from routine protocol. The reduction of tube current caused deterioration of image quality in the white matter. There were no significant differences in the quantitative data in the CBF, CBV and MTT between the conventional perfusion CT and low-radiation-dose perfusion CT.

Conclusions: Low-CTP (1-s inter-scan delay in 40-s data acquisition time, 140 kV tube voltage and 30 mA tube current) produced acceptable image quality and reduced the CTDI remarkably. Dose reduction did not reduce diagnostic information. This protocol is feasible to optimise the radiation protection for patients during dynamic CT study by reducing the radiation dose.

Low-radiation-dose perfusion CT 2: a screening method of neurovascular diseases with multi-detector row CT with 32 detectors

R. Suzuki, H. Itokawa, M. Noda, M. Fujimoto, S. Endo & T. Fujimoto (Department of Neurosurgery, Fujigaoka Hospital, Showa University, Yokohama, Japan)

Background: Multi-detector row computed tomography with 32 detectors (32-MDCT) facilitates acquisition of multiple data sets with each rotation of radiograph tube and scans through large anatomic areas much faster than the single detector CT scanners. We describe a screening method of intra- and extracranial circulation with 32-MDCT to perform perfusion CT and three-dimensional CT angiography simultaneously.

Method: We used a 32-MDCT scanner (Light Speed VCT, GE Medical, Tokyo). Low-radiation-dose perfusion CT protocol (140 kV; 30 mA; eight sections of 8 mm thickness, 1 s inter-scan-delay; 40 s data acquisition) was used to reduce the radiation exposure. 3D-CTA was performed caudal-to-encephalic direction from the aortic arch to circle of Willis at a time.

Results: Only 100 ml non-ionic contrast medium were required to perform all examination including test injection. Studies were performed within 10 min without any adverse effects. The method was capable of evaluating the intra and extra cranial vascular structure and intracranial perfusion parameters simultaneously.

Conclusions: The present system provides several advantages including a detection of intra- and extracranial vascular diseases and intracranial perfusion deficits at a short time, lowering the patient's risk of radiation exposure and improving the medical cost to the consumer.

Operator-dependent variability in cerebral blood flow estimation using computed tomographic perfusion

S. Pushpananthan, V. Petrik & B. A. Bell (Academic Neurosurgery Unit, St George's, University of London, UK)

Background: Computed tomographic perfusion (CTP) uses deconvolution based software to estimate quantitative maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). Operators are required to subjectively define input parameters for the postprocessing calculations. We investigated which of these parameters had the most significant effect on the variability of final CBF values.

Methods: 1728 regions of interest (ROIs) from CTP studies were postprocessed by six operators using GE Medical Systems software. A series of maps was reconstructed by each of the operators by altering the pre- and postenhancement cut-off values, and by using automatic or manual arterial and venous ROI selection. We compared the quantitative values within fixed ROIs derived from each map.

Results: Pearson correlation coefficients were calculated for each operator's manual versus automatic arterial input pairing. The mean Pearson correlation coefficient was 0.78 (range 0.67 – 1.0). Parenchymal ROI correlation coefficients were 0.82 (95% CI 0.76 – 0.89), 0.71 (95% CI 0.60 – 0.82) and 0.84 (95% CI 0.78 – 0.90) for the CBF, CBV and MTT ROIs, respectively. All were significant to a p-value < 0.001.

Conclusions: Variability in the quantification of perfusion defects may influence the clinical interpretation and cause false conclusions to be drawn. The main factor in determining interoperator variability was pre- and postenhancement cut off values. Xenon CT currently remains the better technique for accurate CBF quantification although it is likely that fully automated postprocessing parameter selection will reduce the degree of variability of CTP estimates of CBF.

Perfusion MRI with calculation of the standardised time-to-peak parameter in preoperative diagnosis of idiopathic normal pressure-hydrocephalus

S. Gentzsch¹, C. Našel¹, S. Wolfsberger² & K. Heimberger¹ (¹Division: Neuroradiology—Workgroup for Cerebrovascular Imaging, Department of Radiology, General Hospital, and ²Department of Neurosurgery, General Hospital, Vienna, Austria)

Background: Patient selection for cerebrospinal fluid diversion by implantation of a shunt system is difficult, because idiopathic normal pressure hydrocephalus (NPH) mimics other neurodegenerative disorders and reliable prediction of outcome after shunt surgery is difficult. About 59% of patients improve after shunting, where complications occur in 38% with a 6% combined rate of permanent neurological deficit and death. Perfusion MRI with standardised time-to-peak parameter (stdTTP)[1] provides information of the impaired brain circulation in NPH,[2] therefore being close to possibly underlying pathological mechanisms.

Methods: Perfusion MRI with calculation of stdTTP was performed in 12 consecutive patients before and after shunt surgery. The data were compared with intraventricular pressure measurement, the supposed golden standard, as well as to clinical outcome (Stein-Langfitt score and rapid disability rating scale).

Results: Impairment of perfusion in periventricular white matter before and significant improvement after shunt surgery was found (paired t-test; n = 12; p < 0.05). Improvement of perfusion was more pronounced in patients significantly responding to surgery. The data were in good agreement with intraventricular pressure measurement and clinical testing.

Conclusions: Perfusion-MRI as a non-invasive diagnostic method may support differentiation between patients who will and will not benefit from the implantation of a shunt system.

Dual vessel labelling for regional perfusion imaging

I. Zimine, E. T. Petersen & X. Golay (Department of Neuroradiology, National Neuroscience Institute, Singapore)

Background: Regional perfusion imaging (RPI) is a new technique allowing imaging of individual brain perfusion territories of the major feeding arteries. The method is based on pulsed arterial spin labelling (ASL) and angulated inversion slabs for selective labelling.[1] Three separate scans are needed to obtain flow territories from the left internal carotid artery (LICA), right ICA (RICA) and posterior circulation (POST). We show that the same information can be obtained using two acquisitions where lateral and posterior circulations are labelled simultaneously.

Methods: Individual flow territories from dual vessel labelling scan can be computed in the following manner: where LP/RP are flow maps of left/right ICA and posterior territories. Seven healthy volunteers were scanned on a 3T clinical scanner using the QUASAR sequence[2] for validation. Perfusion maps from the original and dual vessel labelling experiments where obtained using three parameter fit to the general kinetic model. Gray matter regional CBF values were obtained from individually measured and recalculated flow territories.

Results: The flow territories obtained with both labelling schemes were very similar in all subjects. Mean regional CBF averaged across subjects were slightly lower in all territories, although values obtained with dual labelling scheme were not significantly different from those obtained by individual labelling (p > 0.2).

Conclusions: The dual vessel labelling scheme yields identical perfusion territories as the original RPI method with the advantage of reduced scan time and potentially better labelling efficiency.

Metabolic characteristics of irreversibly damaged tissue following head injury

J. P. Coles^1,2, A. S. Cunningham^1,2, R. Salvador², D. A. Chatfield^1,2, T. A. Carpenter², J. D. Pickard^2,3 & D. K. Menon^1,2 (¹Division of Anaesthesia, ²Wolfson Brain Imaging Centre, ³Department of Neurosurgery, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK)

Background: Severe head injury remains a major public health problem with many patients continuing to experience poor outcome. (1) Evidence suggests that there are alterations in cerebral physiology not only within the focal lesions, but also within apparently uninjured brain regions. (2) Improved understanding of the pathophysiological consequences of injury is important for developing and assessing novel neuroprotective strategies, and for predicting outcome.

Methods: Fourteen patients with severe head injury were studied with acute positron emission tomography (PET), and follow-up magnetic resonance (MR) imaging. Regions of irreversible damage were outlined on MR images and applied to coregistered cerebral blood flow (CBF), oxygen utilisation (CMRO₂), cerebral blood volume (CBV) and oxygen extraction fraction (OEF) images. Measurements were compared with non-lesion regions of interest (ROIs), and with control ROIs from controls.

Results: CBF, CMRO₂, CBV and OEF were all significantly lower in lesion ROIs, compared with non-lesion and control ROIs (p < 0.005). The distribution of PET voxel values was greater in patient tissue (lesion and non-lesion), compared with control tissue. Relationships between physiological variables were consistent in controls but disordered in both lesion and non-lesion ROIs. There was considerable heterogeneity of PET variables both between and within patients.

Conclusions: Irreversibly damaged brain has markedly reduced CBF, CMRO₂, CBV and OEF. However, brain regions that appear structurally normal demonstrate pathophysiological derangements when compared with healthy control data. The presence of such abnormal physiology suggests additional neuronal injury that may remain undetected by conventional structural imaging and result in poor outcome.

Defining the glycolytic pathway in traumatic brain injury: a combined microdialysis and FDG-PET study

P. J. Hutchinson^1,3, K. L. Carpenter^1,3, M. T. O'Connell^1,3, A. Seal¹, J. Nortje^2,3, I. Timofeev^1,3, P. G. Al-Rawi¹, J. P. Coles^2,3, T. D. Fryer³, D. K. Menon^2,3 & J. D. Pickard^1,3 (University of Cambridge, Academic Units of ¹Neurosurgery and ²Anaesthesia, and ³Wolfson Brain Imaging Centre, Addenbrooke's Hospital, Cambridge, UK)

Background: Microdialysis continuously monitors the chemistry of a small focal volume of the cerebral extracellular space. Positron emission tomography (PET) establishes metabolism of the whole brain but only for the scan's duration. This study's objective was to apply these techniques together, in patients with traumatic brain injury, to assess the relationship between microdialysis (extracellular glucose, lactate, pyruvate, and the lactate/pyruvate ratio as a marker of anaerobic metabolism) and PET parameters ([18F]-fluorodeoxyglucose; FDG) of glucose metabolism. In particular, we aimed to determine the fate of glucose in terms of differential metabolism to pyruvate and lactate.

Methods: Microdialysis catheters (CMA70 or CMA71) were inserted into the cerebral cortex of 20 patients with major head injury. Microdialysis was performed during FDG-PET scans with regions of interest defined by the location of the gold-tipped microdialysis catheter. Microdialysate analysis was performed on a CMA600.

Results: There was significant linear relationship between the PET-derived parameter of glucose metabolism (cerebral metabolic rate of glucose; CMRglc) and levels of lactate (r = 0.485, p =0.0103) and pyruvate (r = 0.492, p = 0.0092), but not with the lactate/pyruvate ratio.

Conclusions: In this population of patients, glucose was metabolised to both lactate and pyruvate, but was not associated with an increase in the lactate/pyruvate ratio, suggesting a general increase in metabolism, as opposed to a shift towards non-oxidative metabolism.

Clinical significance of diastolic flow velocity in head injured patients

E. A. Schmidt^1,3, M. Czosnyka¹, M. Balestreri², S. Pichnik¹, P. Smielewski¹, B. Matta² & J. D. Pickard¹ (¹Academic Neurosurgery Unit, ²University Department of Anaesthesiology, Addenbrooke's Hospital, Cambridge, UK, and ³Academic Neurosurgery, Hôpital Purpan, Toulouse, France)

Background: After traumatic brain injury, diastolic Flow velocity (FVd) as measured with transcranial Doppler (TCD) is considered to better apprehend cerebral haemodynamics, to be dependent on intracranial pressure and associated with poor outcome.[1],[2] In a large cohort of head injured patients monitored daily with TCD, we correlated FVd with various haemodynamic parameters and outcome.

Methods: We retrospectively analysed data from 236 head injury patients admitted to Addenbrooke's Hospital from 1992 to 2004. Arterial blood pressure (ABP) and intracranial pressure (ICP) were invasively monitored. Flow velocity mean, systolic and diastolic (respectively, FVm, FVs and FVd) and heart rate (HR) were measured daily with TCD for 30 min during the stay in intensive care. Data were averaged to yield one value per parameter per patient. Initial Glasgow coma scale (GCS) and Glasgow outcome scale (GOS) at 6 months were obtained. Regression analysis was performed and Spearman's correlation coefficient was calculated.

Results: As expected FVd was strongly correlated with FVm (r = 0.96) and FVs (r = 0.91). However, FVd was correlated neither with ICP (r = −0.02), ABP (r = 0.03), CPP (r = 0.04), GCS (r = 0) nor GOS (r = −0.06). There was an almost significant positive trend between FVd and HR (r = 0.12, p = 0.06).

Conclusions: Averaged over the time period of stay in intensive care, FVd is not a relevant indicator to estimate high ICP or to predict bad outcome. It seems that FVd is positively correlated with HR, which is sensible as tachycardia diminishes the cardiac diastolic phase and lessens the relaxation period.

Arterial spin labelling: towards quantitative cerebral blood flow measurements

E. T. Petersen, I. Zimine, Y-C. L. Ho & X. Golay (Department of Neuroradiology, National Neuroscience Institute, Singapore)

Background: Obtaining quantitative cerebral blood flow (CBF) using non-invasive arterial spin labelling (ASL) techniques is challenging due to uncertainties in bolus arrival time, arterial-input-function (AIF), underlying kinetics and static tissue parameters like bloods equilibrium-magnetisation (M0b). An ASL technique, capable of measuring the AIF and M0b is proposed for CBF quantification using model-independent deconvolution.

Methods: Using the QUASAR ASL-sequence,[1] AIFs are estimated by subtracting two perfusion-weighted images, acquired respectively with and without vascular crusher-gradients. Knowing the bolus-duration and M0b obtained from a Look-Locker sampled saturation-recovery curve, the local AIF can be scaled and absolute CBF obtained by deconvolution of the tissue perfusion curve by the AIF.[1] M0b estimates based on a corrected blood-brain partition coefficient λ[2] versus a mean was tested. The local ethics committee approved scan of ten healthy volunteers (3T Philips Achieva): TR/TE/ΔTI/TI1 = 4000/23/200/50 ms, 64 × 64 matrix, four slices, FOV = 240 × 240, flip-angle = 30°, SENSE = 2.5. Venc = [∞,3 cm/s], 80 averages.

Results: The CBF values for the volunteers using both the corrected M0b and the traditional M0t/0.9 resulted in mean GM values of: 48.4 ± 1.6 and 41.9 ± 1.4 [ml/100 g/min] (mean ± SEM), respectively. WM: 23.3 ± 1.3 and 24.9 ± 1.5. Notice the change in GM/WM ratio going from 1.7 to 2.1 after λ-correction.

Conclusions: In the present work, a robust method for quantification of CBF has been developed based on simultaneous measurements of AIF, M0 and λ on a voxel-by-voxel basis leading to improved CBF quantification. However, reproducibility tests need to be performed.

MR-perfusion can predict a compromise in cerebrovascular reserve capacity: a correlation study of TTP in MR-perfusion with CBF measurement in stable xenon CT

G. A. Schubert, C. Weinmann, P. Horn & C. Thomé (Department of Neurosurgery, University Hospital Mannheim, University of Heidelberg, Germany)

Background: In order to identify patients eligible for cerebral revascularisation procedures, an extensive preoperative workup is still required. Due to limited availability and potential contraindications for stable xenon CT imaging, MRI may help to discern patients in need of surgical intervention.

Methods: We prospectively evaluated eight patients for standard and high-flow bypass surgery undergoing both MR-perfusion weighted imaging (PWI) and stable xenon-CT (XeCT) measurement. Time-to-peak (TTP) was calculated as the time point of maximum bolus concentration during PWI, and a TTP of 4 s was set as threshold value. Cerebral blood flow (CBF) in XeCT was determined before and after azetazolamide stimulation, and cerebrovascular reserve capacity (CVRC) was considered being compromised when increasing less than 30% of baseline value. A total of 882 regions of interest (ROI) were calculated and anatomically matched.

Results: No correlation could be found for baseline CBF and TTP or CVRC and TTP below threshold. ROIs exhibiting a prolonged TTP showed a significant negative correlation (r = −0.38, p < 0.001) with the calculated CVRC. Differences of CVRC in between groups of TTP < 4 s and > 4 s were highly significant (p < 0.001). While sensitivity at 0.36 was very limited, specificity of PWI to identify ROIs of diminished CVRC was 0.91 at a TTP > 4 s.

Conclusions: While the identification of patients suitable for bypass surgery will remain a diagnostic challenge and XeCT stays the gold standard in this preoperative evaluation, PWI might prove a useful adjunct in cases where XeCT is not available or contraindicated.

Patterns of perfusion alterations in patients with increased intracranial pressure measured with perfusion-MRI, diffusion weighted imaging and diffusion tensor imaging

C. Našel¹, S. Gentzsch¹, S. Wolfberger² & K. Heimberger¹ (¹Division of Neuroradiology—Workgroup for Cerebrovascular Imaging, Department of Radiology, General Hospital, and ²Department of Neurosurgery, General Hospital, Vienna, Austria)

Background: Reduction of cerebral blood flow in patients with acutely or chronically increased intracranial pressure (ICP) is known from measurements using, e.g. SPECT, Perfusion-MRI or Xe-CT. Diffusion alterations in the extracellular compartment in these conditions can be studied with diffusion weighted MRI methods. In this study regional changes of diffusivity in patients with increased ICP was investigated with respect to regional haemodynamic perfusion alterations.

Methods: Totally 31 patients (12 communicating hydrocephalus; 16 subarachnoid haemorrhage; three compensated aquaductal stenosis) were assessed retrospectively for their correlation of regional alterations in (1) perfusion-MRI with calculation of the standardised time-to-peak parameter (stdTTP),[1] (2) diffusion weighted imaging, (3) diffusion tensor imaging (63%)[2] and (4) morphological cerebral changes.

Results: A significant prolongation of stdTTP values in the periventricular white matter regions was found in all groups (ANCOVA, cov.: brain volume; p ≤ 0.05). This was more pronounced in patients with acute ICP increase and communicating hydrocephalus. Patients with acute ICP increase also showed significant reduction of cortical perfusion (ANCOVA, p ≤ 0.05). Diffusion alterations indicating possible remodelling of white matter as measured with diffusion MRI correlated with regional perfusion disturbances and were most clearly depicted in patients with chronic ICP increase.

Conclusions: Despite the small number of patients included, the data suggests a possible correlation of perfusion deficits and white matter changes due to increased ICP. Although the reasons, duration and severeness of ICP in the groups were different, a regional uniform pattern, with highest grade of perfusion and diffusion disturbances in the periventricular zone, was found.

Perfusion and diffusion MR imaging in the differential diagnosis of primary CNS lymphomas from other common cerebral malignant tumours

C. Calli¹, O. Kitis¹, N. Yunten¹, S. Islekel² & T. Akalin³ (Ege University Hospital, Departments of ¹Radiology, ²Neurosurgery, and ³Pathology, Bornova, Izmir, Turkey)

Background: It is sometimes difficult to differentiate primary central nervous system lymphomas (PCNSL) from other common contrast-enhancing malignant tumours of the brain such as glioblastomas, anaplastic astrocytomas and metastases.[1] Our aim was to evaluate the role of perfusion MR imaging (PWI) and diffusion-weighted imaging (DWI) in the differentiation of PCNSL from other contrast-enhancing malignant cerebral tumours.

Methods: Eleven patients with lymphomas were included in the study. As a comparison, contrast-enhancing and histologically proven other brain tumours, 14 anaplastic astrocytomas (AAs), 17 glioblastoma multiformes (GBMs) and nine metastases were also included in the study group. All patients have undergone routine MR examination where DWI and PWI were performed in the same session. DWI was performed with b values of 0, 500, 1000 s/mm[2]. Minimum ADC values (ADC_min) of each tumour was later calculated from ADC map images. PWI was applied using dynamic susceptibility contrast technique and maximum relative cerebral blood volume (rCBVmax) was calculated from each tumour, normalised with contralateral normal white matter. Comparisons of ADC_min and rCBV_max values with the histological types of the enhancing tumours were made with a one-way analysis of variance and Bonferroni test. A p value less than 0.05 indicated a statistically significant difference.

Results: The ADC_min values (mean ± SD) in GBMs, AAs, lymphomas, and metastases were 0.79 ± 0.21 (×10⁻³ mm²/s), 0.75 ± 0.21 (×10⁻³ mm²/s), 0.51 ± 0.09 (×10⁻³ mm²/s), and 0.68 ± 0.11 (×10⁻³ mm²/s), respectively. The difference in ADC_min values were statistically significant between lymphomas and GBMs (p < 0.05). It was also statistically significant between lymphomas and AAs (p < 0.03). However, there were no differences between lymphomas and metastases. The rCBV_max ratio (mean ± SD) in GBMs were 6.33 ± 2.03, whereas it was 3.66 ± 1.79 in AAs, 2.33 ± 0.68 in lymphomas, and 4.45 ± 1.87 in metastases. These values were statistically different between GBMs and lymphomas (p < 0.0001).

Conclusion: Combination of DWI and PWI, with ADC_min and rCBV_max calculations, may aid routine MR imaging in the differentiation PCNSLs from other common cerebral contrast-enhancing malignant tumours.

[1]H magnetic resonance spectroscopy (MRS) to determine the brain-body temperature gradient in healthy human subjects

C. Childs¹, Y. Hiltunen², R. Vidyasagar³ & R. Kauppinen³ (¹Department of Neurosurgery, University of Manchester, UK; ²Environmental Sciences University of Kuopio, Finland; ³School of Sport and Exercise Science, University of Birmingham, UK)

Background: It is often assumed that injured brain is ‘hotter’ than the body, with core (T_c) exceeding brain temperature (T_brain) by as much as 2°C in some cases. Recent observations in patients with primary traumatic brain injury (TBI)[1] do not support a large, positive, brain-body temperature gradient (ΔT_brain– T_body). The aim of the study was to investigate the ΔT_brain– T_body in healthy subjects under normal physiological conditions.

Methods: MRI and MRS were performed at 3T. Single voxel, ¹H MR spectra were acquired from four brain regions, including the region within grey/white matter where intraparenchymal sensors are customarily sited. T_c was measured at the start and end of scanning.

Results: Eight healthy adults (five males) aged 23 – 52 years were studied at 20°C for 40 min. T_c, 36.5 – 37.2°C (median 36.8°C) remained unchanged throughout the study. In brain, the ¹H MRS spectra from single voxels ranged from 34.9 to 37.1°C (median 36.5°C). There was no systematic difference in temperature between the regions. Overall mean (SD) T_brain[36.3(0.3)°C] was significantly lower than T_c[36.8(0.2)°C, p < 0.001]. ΔT_brain– T_body ranged from −0.8 to −0.1°C (median −0.5°C).

Conclusions: Use of the ¹H chemical shift difference of water and the brain metabolite N-acetylaspartate (NAA) to determine brain temperature has helped clarify the gradient between brain and body temperature in healthy humans, and will help us to better understand the significance of changes in the magnitude and direction of the brain-body temperature gradient after TBI.

Oxygen metabolic mapping by MRI-BOLD technique

A. Shiino, S. Abe & M. Matsuda (Department of Neurosurgery, Shiga University of Medical Science, Japan)

Background: Evaluation of regional oxygen metabolism of the brain in acute ischaemia provides useful information for salvage of penumbral area, but PET is the only available method for this purpose at present. We carried out a preliminary study to develop a new approach by using MR imaging.

Methods: We used the equations proposed by Davis et al.[1]: where M is dependent on tissue dHb content. If CMRO₂ is not affected by acetazolamide administration, we can get rCMRO₂ value from the following equation: α and β come from the following equations:, 1/T2* = C(1 –Y) βCBVV, where Y is venous blood oxygenation level and CBVV is venous cerebral blood volume. Here, we set α = 0.38 and β = 1.5. Pairs of BOLD and CBF measurements were performed in five patients with large vessel occlusion. We used Ostargaad's algorithm[2] for CBF measurements. We measured venous output function from the sagittal sinus to correct the partial volume effect of arterial input function (AIF). For verification of the results, the patients also underwent PET study.

Results: There was reasonable grey/white contrast in the rCMRO₂ map obtained by BOLD/perfusion methods in all patients. In a patient with left MCA occlusion, the area of lowered rCMRO₂ seemed to be in agreement with that of the PET.

Conclusions: We showed that oxygen metabolism could be visualised on the map by the combination of CBF and BOLD measurements. Although careful verification is necessary, this technique has a potential for clinical use.

Diagnosis of early stage of cerebral infarction on CT scan: our new device of image filter

H. Nakamura, R. Nakashima, A. Tanaka & K. Urahama (Departments of Radiology & Neurosurgery, Fukuoka University, Chikushi Hospital, Fukuoka, Japan)

Background: Diagnosis of early stage of cerebral infarction on CT scan is crucial to make a decision of therapeutic strategies. However, it has been hampered by a small difference of CT values between normal tissue and infracted tissue in early stage.[1] Therefore, it is mandatory to intensify the small difference of CT values on CT images, contrasting normal and infracted tissue.

Methods: The brains of the patients with early stage of cerebral infarction have been scanned by CT Scanner (Toshiba, Japan. 120 kv, 250 mAS, 1.0 s, FC22). Area of 5 × 5 pixels was placed around the suspected lesion. The pixel values in the area were averaged and the area was divided into two portions whose values were above or below the average. The values of the larger portion were adopted as those of the whole area. CT images, converted by this method, were treated by contrast-enhancement.

Results: CT detection of cerebral infarction in acute stage was facilitated by our new device of image filter.

Conclusions: It is a problem that space resolution of CT scan is sacrificed in this method. Further improvement must be undertaken.

Physiological imaging of cerebral tumours with blood-brain barrier permeability CT: impact on radiotherapy target volumes

J. Reardon, K. Miles, A. Chalmers & R. Simcock (Brighton and Sussex University Hospitals NHS Trust, Eastern Road, Brighton UK)

Aim: Treatment planning paradigms in radiation oncology are increasingly incorporating physiological imaging techniques. This pilot study evaluates the potential for CT-derived maps of blood-brain barrier permeability (BBBP) to modify radiotherapy target volumes (TVs) for cerebral tumours.

Technique: Images of BBBP were derived for six cerebral tumours by mathematically modelling the temporal changes in enhancement in a dynamic series of CT images obtained following intravenous administration of conventional contrast material. Two radiation oncologists constructed TVs using conventional CT images initially followed by BBBP images. The impact of BBBP images on the size and position of TVs and inter-observer consistency were assessed.

Results: TVs constructed on BBBP images tended to be smaller (change in size – 43 to + 33%, median −19%, p = 0.06). TVs constructed on BBBP images were displaced by 1.6 – 24% (median 11.5%) of the mean TV diameter. The use of BBBP imaging did not reduce inter-observer variation.

Conclusions: BBBP imaging with CT can be used to incorporate physiological imaging into radiotherapy planning of cerebral tumours with the potential to improve tumour targeting without the need for additional imaging devices.

Early radiotherapy dose response in normal brain tissue: a sequential perfusion MRI study

S. J. Price^{1 – 3}, R. Jena⁴, H. A. L. Green³, N. Kirkby^4,5, C. Coles⁴, J. D. Pickard^1,3, J. H. Gillard² & N. G. Burnet⁴ (¹Academic Neurosurgery Unit, ²University Department of Radiology, ³Wolfson Brain Imaging Centre, and ⁴University Department of Oncology, Cambridge University and Addenbrooke's Hospital, Cambridge, and ⁵Fluids Research Centre, School of Engineering, University of Surrey, Guildford, Surrey, UK)

Background: In the brain there are no accurate methods for assessment of radiation-induced normal tissue injury at a level below frank brain necrosis. Changes in cerebral perfusion have been demonstrated as a late effect of radiation therapy. In this pilot study we assess the feasibility of a non-invasive magnetic resonance imaging technique for the assessment of early dose-dependent change in cerebral perfusion parameters.

Methods: Four patients undergoing conformal radiotherapy to 54 Gy in 30 fractions for low-grade gliomas were imaged with conventional T2-weighted and fluid attenuated inversion recovery (FLAIR) imaging as well as dynamic contrast susceptibility perfusion imaging. Forty regions of interest were determined from the periventricular white matter. Patients were imaged before radiotherapy, after one fraction, at the end of treatment and then at 1 and 3 months from the end of radiotherapy. For each region the relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and mean transit time (MTT) expressed as a ratio of the baseline value, and radiotherapy dose was determined.

Results: Regions within the 80% isodose demonstrated a reduction in rCBV and rCBF over the 3-month period. There was no significant alteration in rCBV or rCBF in regions outside the 60% isodose (i.e. <32 Gy). MTT did not alter in any region. There appears to be a threshold effect over all time points for rCBV and rCBF at the 55 – 60% isodose (i.e. approximately 30 Gy) below which no effect was found.

Conclusions: There is a dose-related reduction of rCBV and rCBF in normal brain following radiotherapy at higher dose levels. MR perfusion imaging is a non-invasive method that appears to act as a marker of sub-clinical response of normal brain.

Asymptomatic individuals can harbour vulnerable carotid atheroma: a USPIO-enhanced magnetic resonance imaging study

S. Howarth¹, R. Trivedi², T. Tang¹, M. J. Graves¹, P. J. Kirkpatrick² & J. H. Gillard¹ (¹University Department of Radiology, and ²Academic Department of Neurosurgery, Addenbrooke's Hospital, Cambridge, UK)

Background: Vulnerable carotid atheroma has the histological features of a thin fibrous cap, extensive lipid core and high macrophage burden, often localised to the shoulder regions of the plaque. This inflammation can be imaged non-invasively using high resolution MR imaging enhanced with Sinerem, an ultrasmall superparamagnetic iron oxide (USPIO) contrast agent. The asymptomatic carotid surgery trial suggested a benefit from endarterectomy with a stenosis of 70% or greater and therefore implies a cohort of asymptomatic individuals with vulnerable plaque who would benefit from intervention.

Methods: Ten patients with asymptomatic carotid stenosis underwent multisequence imaging at 1.5 T pre- and 36 h post-USPIO infusion. Plaques were retrieved for histological analysis and stained for iron (Perls), macrophages (CD68 and MAC387) and other morphological features (H&E and EVG). Images were manually segmented into quadrants and focal regions showing signal drop post USPIO (CMR Tools) and co-registered, where possible, with histological sections. Signal drop when normalised to adjacent muscle was calculated for all quadrants and focal regions.

Results: There were eight males and the mean age was 73 (asymptomatics). Patients had a mean stenosis of 72% (range 50 – 80%). 32% of image quadrants (four patients) showed a significant signal drop post USPIO infusion and 27% of images exhibited focal signal drop. These areas correlated with macrophage populations assessed histologically following endarterectomy with most found in the shoulder regions of the plaque.

Conclusions: The study suggests that approximately one-third of patients with asymptomatic carotid stenosis harbour vulnerable, inflamed plaque. Luminal stenosis is an inadequate predictor of risk in this group and non-invasive characterisation of inflammatory burden using USPIO-enhanced MR imaging may improve patient selection for subsequent intervention, whilst minimising unnecessary morbidity in those patients with stable plaque.

Comparison of three ways to measure Mx and PRx in neurocritical patients

C. Puppo¹, L. Moraes¹, J. Camacho², B. Yelicich², H. Gomez² & A. Biestro¹ (¹ICU, Hospital de Clínicas, and ²Laboratorio de Acústica Ultrasonora, Instituto de Física, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay)

Background: Cerebral autoregulation and vasoreactivity studies have shifted towards indexes obtained from spontaneous oscillations of blood pressure (ABP): Mx and Prx.[1],[2] Authors developed a software tool for indexes measurement (‘Contine’). Its use raised some questions: (1) should the 4 min moving intervals be measured without overlapping values, or should they overlap, shifting every 4 s? (2) It is accepted that ΔCPP must be >5 mmHg to trigger cerebral autoregulatory mechanism. Are these oscillations present in every patient?

Methods: ABP, intracranial pressure (ICP) and cerebral blood flow velocity (CBFV) were continuously monitored at a frequency of 50 Hz in 11 patients, 10 males, age range 17 – 61 years; severe TBI (8), subarachnoid haemorrhage (2) and ventriculitis (1).Three values for Mx and Prx (1, 2 and 3) were calculated and compared for each patient, averaging the correlation coefficients obtained from each 4 min interval: (1) without overlapping (Mx1 and Prx1); (2) overlapping them, irrespective of the change in cerebral perfusion pressure (ΔCPP; Mx2 and Prx2; the present standard); and (3) overlapping intervals, excluding those with ΔCPP < 5 mmHg (Mx3 and Prx3).

Results: The methods showed good agreement in nine out of eleven patients (Bland and Altman plot). However, a no oscillatory flow pattern was seen in a patient, with every interval ΔABP < 5 mmHg, and another one showed a significant difference between the no overlapping-overlapping indexes.

Conclusions: Overlapping intervals should be used. Patients should be screened to identify and exclude intervals with a ΔCPP < 5 mmHg. In some cases a hypertensive challenge is necessary.

Brain attack—CT perfusion in the diagnosis and management of acute ischaemic stroke

R. Farmer (Department of Radiology, Addenbrooke's Hospital, Cambridge, UK)

The phrase heart attack is used by the general public to describe acute myocardial infarction. Everyone knows that people with sudden severe chest pain need to be rushed to hospital for emergency treatment. Following a successful trial of treating acute ischaemic stroke patients with intravenous tissue plasminogen activator, the management of acute stroke patients is now similar to the medical emergency of an MI and the term ‘brain attack’ may become common parlance.

At Addenbrooke's Hospital we offer a fast track CT service for patients fitting the criteria to receive TPA. This includes CT perfusion scanning in order to define areas of at risk, but still salvageable brain tissue.

This presentation shared intramural experience gained in being part of the emergency stroke team, in a hospital very pro-active in acute stroke treatment, including:

• background to treatment of stroke with tissue plasminogen activator;

• method of CT perfusion scanning;

• interpretation of perfusion images;

• technique of intra-arterial thrombolysis;

• case presentation.

Utilisation of dynamic CT perfusion in the study of intracranial meningiomas and its surrounding tissue

Z. Hussain, I. Sergides, S. Naik, C. Good, K. Miles & G. Critchley (Department of Neurosciences, Hurstwood Park Neurological Centre, Brighton & Sussex University Hospitals, UK)

Aim: To use CT perfusion (CTP) to assess levels of ischaemia in brain areas around intracranial meningiomas.

Materials and methods: Fifteen patients with intracranial meningiomas were analysed pre-operatively with CTP study. The cerebral blood flow (CBF), cerebral blood volume (CBV) and time to peak (TTP) were measured in the tumour, peritumoural oedema and in the normal areas of brain.

Results: The peritumoural oedema measured a mean CBF of 17.36 ml/min/100 ml (median = 15.8) and the mean CBF value in the whole tumour was 93.86 ml/min/100 ml (median = 79.9). The mean CBV measured in the peritumoural oedema was 2.7(median = 2.3) and the measured mean CBV of the tumour was 15 (median = 13.2). In the region of the peritumoural oedema the mean CBF and CBV were lower than in the tumour bed. Normal brain remote from the tumour measured less CBF (mean = 28.36 ml/min/100 ml, median = 29.7) and CBV (mean = 4.1, median = 3.8) than the tumour. Six patients were noted to have CBF of less than 15 ml/min/100 ml in the perilesional oedema. The measured mean CBF and CBV in the normal area of brain was higher than in the peritumoural oedema, while the TTP was greater in the perilesional oedema (mean = 11, median = 10.4) when compared with areas of normal brain (mean = 9.9, median = 9.5) with statistically significant p-values.

Conclusion: The values obtained elucidate the fact that perilesional oedema are areas that are ischaemic. By subset analysis it may be possible to identify those areas with recoverable tissue from non-recoverable tissue.

A comparison of CT and MRI perfusion studies in patients with glioma

A. Varma, A. R. Brodbelt, M. Jenkinson & E. T. Smith (Department of Neurosurgery and Neuroradiology, Walton Centre, Liverpool, UK)

Background: Perfusion studies are used in the treatment and assessment of patients with brain tumours to provide information on the aggression and vascularity of the tumour. Both CT and MRI are used to provide this information but there is little in the way of formal comparison. Furthermore, the routine clinical use of perfusion study data demands a rapid and reproducible measure of assessment.

Methods: Fifty patients with cerebral glioma were examined. Each patient had CT and MRI perfusion, single voxel MRS, standard brain MRI and biopsy proven assessment of tumour grade. Perfusion was measured by visual inspection of the images and compared with a quantitative measurement of a specified region of interest. Patients were followed up to 4 years post study.

Results: There was agreement in 41 of the 50 cases between CT and MR perfusion studies when the standard visual assessment of the images was performed. Quantifying small regions of interest improved correlation. High grade lesions (grade 3 and 4) had a higher perfusion on both CT and MR than low grade lesions (p < 0.001), and demonstrated contrast enhancement (p < 0.001). There was no relationship between Cho/NAA and perfusion or tumour grade.

Conclusions: Both CT and MR provide perfusion data that correlates with tumour grade. Cho/NAA ratio was not helpful in predicting tumour grade in this group of patients. Routine CT or MR perfusion has a role in the management of patients with cerebral gliomas. A rapid visual assessment is not as reliable as measurements of a region of interest.