Nazia P. Saeed

Regional Differences in Dynamic Cerebral Autoregulation in the Healthy Brain Assessed by Magnetic Resonance Imaging

A novel method is described for mapping dynamic cerebral blood flow autoregulation to assess autoregulatory efficiency throughout the brain, using magnetic resonance imaging (MRI). Global abnormalities in autoregulation occur in clinical conditions, including stroke and head injury, and are of prognostic significance. However, there is limited information about regional variations. A gradient-echo echo-planar pulse sequence was used to scan the brains of healthy subjects at a rate of 1 scan/second during a transient decrease in arterial blood pressure provoked by a sudden release of pressure in bilateral inflated thigh cuffs. The signal decrease and subsequent recovery were analyzed to provide an index of autoregulatory efficiency (MRARI). MRI time-series were successfully acquired and analyzed in eleven subjects. Autoregulatory efficiency was not uniform throughout the brain: white matter exhibited faster recovery than gray (MRARI = 0.702 vs. 0.672, p = 0.009) and the cerebral cortex exhibited faster recovery than the cerebellum (MRARI = 0.669 vs. 0.645, p = 0.016). However, there was no evidence for differences between different cortical regions. Differences in autoregulatory efficiency between white matter, gray matter and the cerebellum may be a result of differences in vessel density and vasodilation. The techniques described may have practical importance in detecting regional changes in autoregulation consequent to disease.

Measurement of cerebral blood flow responses to the thigh cuff maneuver: a comparison of TCD with a novel MRI method

Cerebral autoregulation (CA) describes the mechanism responsible for maintaining cerebral blood flow (CBF) relatively constant, despite changes in mean arterial blood pressure (ABP). This paper introduces a novel method for assessing CA using magnetic resonance imaging (MRI). Images are rapidly and repeatedly acquired using a gradient-echo echo-planar imaging pulse sequence for a period of 4minutes, during which a transient decrease in ABP is induced by rapid release of bilateral thigh cuffs. The method was validated by comparing the observed MRI signal intensity change with the CBF velocity change in the middle cerebral arteries, as measured by transcranial Doppler (TCD) ultrasound, using a standardized thigh cuff maneuver in both cases. Cross-correlation analysis of the response profiles from the left and right hemispheres showed a greater consistency for MRI measures than for TCD, both for interhemisphere comparisons and for repeated measures. The new MRI method may provide opportunities for assessing regional autoregulatory changes following acute stroke, and in other conditions in which poor autoregulation is implicated.

The Leicester cerebral haemodynamics database: normative values and the influence of age and sex

Normative values of physiological parameters hold significance in modern day clinical decision-making. Lack of such normative values has been a major hurdle in the translation of research into clinical practice. A large database containing uniform recordings was constructed to allow more robust estimates of normative ranges and also assess the influence of age and sex. Doppler recordings were performed on healthy volunteers in the same laboratory, using similar protocols and equipment. Beat-to-beat blood pressure, heart-rate, electrocardiogram, and end-tidal CO2 were measured continuously. Bilateral insonation of the middle cerebral arteries (MCAs) was performed using TCD following a 15 min stabilisation, and a 5 min baseline recording. Good quality Doppler recordings for both MCAs were obtained in 129 participants (57 female) with a median age of 57 years (range 20-82). Age was found to influence baseline haemodynamic and transfer function analysis parameters. Cerebral blood flow velocity and critical closing pressure were the only sex-related differences found, which was significantly higher in females than males. Normative values for cerebral haemodynamic parameters have been defined in a large, healthy population. Such age/sex-defined normal values can be used to reduce the burden of collecting additional control data in future studies, as well as to identify disease-associated changes.

Meta-analysis of Vascular Imaging Features to Predict Outcome Following Intravenous rtPA for Acute Ischemic Stroke.

Background The present review investigated which findings in vascular imaging techniques can be used to predict clinical outcome and the risk of symptomatic intracerebral hemorrhage (sICH) in patients who underwent intravenous thrombolytic treatment. Methods Publications were searched, and the inclusion criteria were as follows: (1) published manuscripts, (2) patients with acute ischemic stroke managed with intravenous recombinant tissue plasminogen activator (rtPA), and (3) availability of imaging assessment to determine vessel patency or the regulation of cerebral blood flow prior to, during, and/or after thrombolytic treatment. Clinical outcomes were divided into neurological outcome [National Institutes of Health Stroke Scale (NIHSS) within 7 days] and functional outcome (modified Rankin score in 2–3 months). sICH was defined as rtPA-related intracerebral bleeding associated with any worsening of NIHSS. Results Thirty-nine articles were selected. Recanalization was associated with improved neurological and functional outcomes (OR = 7.83; 95% CI, 3.71–16.53; p < 0.001 and OR = 11.12; 95% CI, 5.85–21.14; p < 0.001, respectively). Both tandem internal carotid artery/middle cerebral artery (ICA/MCA) occlusions and isolated ICA occlusion had worse functional outcome than isolated MCA occlusion (OR = 0.26, 95% CI, 0.12–0.52; p < 0.001 and OR = 0.24, 95% CI, 0.07–0.77; p = 0.016, respectively). Reocclusion was associated with neurological deterioration (OR = 6.48, 95% CI, 3.64–11.56; p < 0.001), and early recanalization was associated with lower odds of sICH (OR = 0.36, 95% CI, 0.18–0.70; p = 0.003). Conclusion Brain circulation data before, during, and after thrombolysis may be useful for predicting the clinical outcome. Cerebral arterial recanalization, presence and site of occlusion, and reocclusion are all important in predicting the clinical outcome.

The Carotid Artery as an Alternative Site to the Middle Cerebral Artery for Reproducible Estimates of Autoregulation Index.

Temporal insonation is not always possible for the middle cerebral artery (MCA) for blood flow velocity (BFV) measurements, to estimate cerebral autoregulation. We compared BFV and cerebral autoregulation estimates from the common-carotid (CCA) and internal-carotid arteries (ICA) with the MCA. BFV was measured at the CCA, ICA and MCA, synchronously with blood pressure, heart rate and end-tidal CO2 and was recorded onto a data acquisition system. The autoregulation index (ARI) estimated using the Tiecks model. Eleven healthy volunteers (7 women, 33 ± 9 years old) were recruited. BFVs in the MCA, CCA and ICA were 60.3 ± 8.9, 64.4 ± 6.5 and 69.2 ± 4.8 cm/s, respectively. ARI estimates were not significantly different (5.6 ± 0.8, 6.0 ± 1.1 and 5.9 ± 0.5, respectively). Good reproducibility over repeated measurements was evidenced by low coefficient of variation of standard error of measurement for BFV and ARI. The CCA and ICA are alternatives to the MCA, where insonation is impossible, because of an absent trans-temporal window or where it cannot be tolerated, such as in patients with head injury.

Dynamic cerebral autoregulation following acute ischaemic stroke: Comparison of transcranial Doppler and magnetic resonance imaging techniques

Novel MRI-based dynamic cerebral autoregulation (dCA) assessment enables the estimation of both global and spatially discriminated autoregulation index values. Before exploring this technique for the evaluation of focal dCA in acute ischaemic stroke (AIS) patients, it is necessary to compare global dCA estimates made using both TCD and MRI. Both techniques were used to study 11 AIS patients within 48 h of symptom onset, and nine healthy controls. dCA was assessed by the rate of return of CBFV (Rturn) following a sudden drop induced by the thigh cuff manoeuvre. No significant between-hemisphere differences were seen in controls using either the TCD or MRI technique. Inter-hemisphere averaged Rturn values were not different between TCD (1.89 ± 0.67%/s) and MRI (2.07 ± 0.60%/s) either. In patients, there were no differences between the affected and unaffected hemispheres whether assessed by TCD (Rturn 0.67 ± 0.72 vs. 0.98 ± 1.09%/s) or MRI (0.55 ± 1.51 vs. 1.63 ± 0.63%/s). Rturn for both TCD and MRI was impaired in AIS patients compared to controls in both unaffected and affected hemispheres (ANOVA, p = 0.00005). These findings pave the way for wider use of MRI for dCA assessment in health and disease.

Cerebrovascular effects of the thigh cuff maneuver

Arterial hypotension can be induced by sudden release of inflated thigh cuffs (THC), but its effects on the cerebral circulation have not been fully described. In nine healthy subjects [aged 59 (9) yr], bilateral cerebral blood flow velocity (CBFV) was recorded in the middle cerebral artery (MCA), noninvasive arterial blood pressure (BP) in the finger, and end-tidal CO2 (ETCO2) with nasal capnography. Three THC maneuvers were performed in each subject with cuff inflation 20 mmHg above systolic BP for 3 min before release. Beat-to-beat values were extracted for mean CBFV, BP, ETCO2 , critical closing pressure (CrCP), resistance-area product (RAP), and heart rate (HR). Time-varying estimates of the autoregulation index [ARI(t)] were also obtained using an autoregressive-moving average model. Coherent averages synchronized by the instant of cuff release showed significant drops in mean BP, CBFV, and RAP with rapid return of CBFV to baseline. HR, ETCO2 , and ARI(t) were transiently increased, but CrCP remained relatively constant. Mean values of ARI(t) for the 30 s following cuff release were not significantly different from the classical ARI [right MCA 5.9 (1.1) vs. 5.1 (1.6); left MCA 5.5 (1.4) vs. 4.9 (1.7)]. HR was strongly correlated with the ARI(t) peak after THC release (in 17/22 and 21/24 recordings), and ETCO2 was correlated with the subsequent drop in ARI(t) (19/22 and 20/24 recordings). These results suggest a complex cerebral autoregulatory response to the THC maneuver, dominated by myogenic mechanisms and influenced by concurrent changes in ETCO2 and possible involvement of the autonomic nervous system and baroreflex.

Are Hand-Held TCD Measurements Acceptable for Estimates of CBFv?

Cerebral blood flow velocity (CBFv) and the autoregulation index (ARI) can be reproducibly assessed by noninvasive transcranial Doppler (TCD) methodology using frame-held (FH) ultrasound probes. However, FH techniques may be impractical in severe head injury patients and neonates, where CBFv and ARI estimates are an important component of clinical assessment and management. Therefore, the aim of this study was to investigate the feasibility of an alternative hand-held (HH) approach to CBFv and ARI measurement. In a healthy volunteer population of 11 subjects, mean age 37 years, CBFv and ARI estimates were not significantly different between HH and FH acquisition techniques. In addition, in the hands of a single observer, good reproducibility over two visits, a mean of 6 days apart, was observed: intra-visit coefficient of variation (CV) 5.3% and 15.8%; and intraclass correlation coefficient (ICC) 0.8 and 0.4 for CBFv and ARI, respectively. Further work is required to assess the use of alternative sites to the middle cerebral artery (MCA) for the assessment of CBFv and ARI using HH rather than FH techniques and the applicability of this methodology in patient populations.

The carotid artery as an alternative site for dynamic autoregulation measurement: an inter-observer reproducibility study

The internal carotid artery (ICA) has been proposed as an alternative site to the middle cerebral artery (MCA) to measure dynamic cerebral autoregulation (dCA) using transcranial Doppler ultrasound (TCD). Our aim was to test the inter-operator reproducibility of dCA assessment in the ICA and the effect of interaction amongst different variables (artery source × operator × intra-subject variability). Two operators measured blood flow velocity using TCD at the ICA and MCA simultaneously on each side in 12 healthy volunteers. The autoregulation index (ARI) was estimated by transfer function analysis. A two-way repeated measurements ANOVA with post-hoc Tukey tested the difference between ARI by different operators and interaction effects were analysed based on the generalized linear model. In this healthy population, no significant differences between operator and no interaction effects were identified amongst the different variables. This study reinforced the validity of using the ICA as an alternative site for the assessment of dCA. Further work is needed to confirm and extend our findings, particularly to disease populations.

Increasing the Contrast-to-Noise Ratio of MRI Signals for Regional Assessment of Dynamic Cerebral Autoregulation

OBJECTIVE To devise an appropriate measure of the quality of a magnetic resonance imaging (MRI) signal for the assessment of dynamic cerebral autoregulation, and propose simple strategies to improve its quality. MATERIALS AND METHODS Magnetic resonance images of 11 healthy subjects were scanned during a transient decrease in arterial blood pressure (BP). Mean signals were extracted from non-overlapping brain regions for each image. An ad-hoc contrast-to-noise ratio (CNR) was used to evaluate the quality of these regional signals. Global mean signals were obtained by averaging the set of regional signals resulting after applying a Hampel filter and discarding a proportion of the lower quality component signals. RESULTS Significant improvements in CNR values of global mean signals were obtained, whilst maintaining significant correlation with the original ones. A Hampel filter with a small moving window and a low rejection threshold combined with a selection of the 50% component signals seems a recommendable option. CONCLUSIONS This work has demonstrated the possibility of improving the quality of MRI signals acquired during transient drops in BP. This approach needs validation at a voxel level, which could help to consolidate MRI as a technological alternative to the standard techniques for the study of cerebral autoregulation.