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.

Does stroke subtype and measurement technique influence estimation of cerebral autoregulation in acute ischaemic stroke?

BACKGROUND: It is known that dynamic cerebral autoregulation (dCA) is acutely impaired following ischaemic stroke (IS). However, the influence of stroke subtype, the affected (AF) and unaffected (UA) hemispheres, and the effects of a methodological approach on dCA estimates in stroke are all inconclusive. Therefore, we studied cortical and subcortical acute IS (AIS) patients to test the primary hypotheses that (1) dCA is impaired in stroke subtypes when compared to controls, (2) dCA impairment is more pronounced in the AF compared with the UA hemisphere, and (3) similar results are obtained with both spontaneous blood pressure (BP) fluctuation techniques, and sudden induced BP changes by thigh cuff deflation. METHODS: We assessed the dCA values in AIS patients and in healthy controls (n = 10). The AIS patient group consisted of anterior circulation cortical (n = 11) and subcortical (n = 11) strokes within 48 h of symptom onset. Cerebral blood flow velocity was measured using transcranial Doppler ultrasound, and BP measurements were recorded before, during and after the release of bilateral thigh cuffs in 10 controls (7 males) of a mean age of 59 ±15 years (range 31-75), 11 cortical strokes (7 males) of a mean of age 65 ± 19 years (range 25-88) and 11 subcortical strokes (7 males) of a mean age of 60 ± 18 years (range 39-85). Autoregulation index (ARI) estimates, calculated using spontaneous fluctuations and thigh cuff manoeuvre, were derived. Differences in ARI (Tiecks' model) were tested with repeated-measures ANOVA. RESULTS: A total of 22 patients were included, comprising 11 subcortical (lacunar clinical syndrome) and 11 cortical strokes (total anterior circulation stroke/partial anterior circulation syndrome). Of the 10 control subjects, 1 later withdrew because of intolerance to the thigh cuffs. Similar ARI estimates were obtained in both groups, whether assessed from spontaneous fluctuations or thigh cuff measurements (p = 0.37). ARI differences were not significantly different between hemispheres for both control and stroke populations. ARI was significantly impaired in AIS patients compared to age-, sex- and BP-matched control subjects, with a greater impairment of dCA observed in cortical IS. CONCLUSIONS: The results of this study suggest that both spontaneous fluctuations and thigh cuff deflation techniques are able to provide reliable estimates of ARI, with the estimates from both spontaneous fluctuations and thigh cuff deflation techniques being in keeping with those reported elsewhere in the literature. dCA was impaired following AIS compared to controls when stroke subtype was considered. Importantly, no differences were observed between UA and AF. This has implications for the assessment of CA after stroke and reinforces the need to define a 'gold standard' test for the investigation of CA.

Contribution of vascular and neural segments to baroreflex sensitivity in response to postural stress.

BACKGROUND/AIMS: The baroreflex pathway has a vascular and a neural segment, both being modulated by variations in peripheral blood pressure (BP). Besides overall baroreceptor sensitivity (BRS), defined as the spectral relationship between changes in peripheral BP and R-R interval within the frequency band of 0.05-0.15 Hz, vascular and neural segment contributions to the overall BRS can be distinguished. We test the hypothesis that changes in overall BRS following a postural maneuver mainly originate from the vascular (peripheral pressure to carotid artery diameter) rather than the neural segment (carotid artery diameter to R-R interval). METHODS: Peripheral pressure (Finapress), carotid artery diameter (ultrasound in B-/M-mode) and electrocardiogram values of 20 young subjects in supine and upright-seated postures were recorded simultaneously. Transfer gains were computed for the segmental and overall responses. RESULTS: Postural change significantly increases peripheral BP and carotid artery diameter. The vascular segment has a uniform spectral distribution. Statistical analyses revealed that postural change decreased overall (p < 0.004) and vascular (p < 0.0001) transfer gains, but did not modify neural gain. CONCLUSIONS: Unlike the neural segment, the vascular segment is frequency non-specific. The decrease in overall BRS due to a postural change is mainly explained by the reduced transfer gain of the vascular segment.

Can we assess dynamic cerebral autoregulation in stroke patients with high rates of cardiac ectopicity?

It is unclear whether physiological recordings containing high numbers of ectopic heartbeats can be used to measure the cerebral autoregulation (CA) of blood flow. This study evaluated the utility of such data for assessing dynamic CA capacity. Physiological recordings of cerebral blood flow velocity, heart rate, end-tidal CO2 and beat-to-beat blood pressure from acute ischaemic stroke (AIS) patients (n = 46) containing ectopic heartbeats of varying number (0.2 to 25 occurrences per minute) were analysed. Dynamic CA was determined using the autoregulation index (ARI) and the normalised mean square error (NMSE) was used to evaluate the fitting of the step response between BP and CBFV to Tiecks' model. We fitted linear mixed models on the CA variables incorporating ectopic burden, age, sex and hemisphere as predictor variables. Ectopic activity demonstrated an association with mean coherence (p = 0.006) but not with ARI (p = 0.162), impaired CA based on dichotomised ARI (p = 0.859) or NMSE (p = 0.671). Dynamic CA could be reliably assessed in AIS patients using physiological recordings with high rates of cardiac ectopic activity. This provides supportive data for future studies evaluating CA capability in AIS patients, with the potential to develop more individualised treatment strategies. Graphical Abstract.

Cerebral Haemodynamics following Acute Ischaemic Stroke: Effects of Stroke Severity and Stroke Subtype.

BACKGROUND: Acute ischaemic stroke (AIS) patients often show impaired cerebral autoregulation (CA). We tested the hypothesis that CA impairment and other alterations in cerebral haemodynamics are associated with stroke subtype and severity. METHODS: AIS patients (n = 143) were amalgamated from similar studies. Data from baseline (< 48 h stroke onset) physiological recordings (beat-to-beat blood pressure [BP], cerebral blood flow velocity (CBFV) from bilateral insonation of the middle cerebral arteries) were calculated for mean values and autoregulation index (ARI). Differences were assessed between stroke subtype (Oxfordshire Community Stroke Project [OCSP] classification) and severity (National Institutes of Health Stroke Scale [NIHSS] score < 5 and 5-25). Correlation coefficients assessed associations between NIHSS and physiological measurements. RESULTS: Thirty-two percent of AIS patients had impaired CA (ARI < 4) in affected hemisphere (AH) that was similar between stroke subtypes and severity. CBFV in AH was comparable between stroke subtype and severity. In unaffected hemisphere (UH), differences existed in mean CBFV between lacunar and total anterior circulation OCSP subtypes (42 vs. 56 cm•s-1, p < 0.01), and mild and moderate-to-severe stroke severity (45 vs. 51 cm•s-1, p = 0.04). NIHSS was associated with peripheral (diastolic and mean arterial BP) and cerebral haemodynamic parameters (CBFV and ARI) in the UH. CONCLUSIONS: AIS patients with different OCSP subtypes and severity have homogeneity in CA capability. Cerebral haemodynamic measurements in the UH were distinguishable between stroke subtype and severity, including the association between deteriorating ARI in UH with stroke severity. More studies are needed to determine their clinical significance and to understand the determinants of CA impairment in AIS patients.

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.

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 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.

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.

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.

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 4 minutes, 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.