Ronney Panerai | University of Leicester (original) (raw)

Papers by Ronney Panerai

Neurosurgical Review

There has been renewed interest in decompressive craniectomy as a surgical treatment for elevated... more There has been renewed interest in decompressive craniectomy as a surgical treatment for elevated intracranial pressure (ICP), although evidence-based clinical data are still lacking and some experimental results are conflicting. Ongoing clinical trials on the use of this operation after traumatic brain injury (TBI) may clarify the clinical application of this technique, however, some pathophysiological issues, such as the timing of this operation, its effect on brain edema formation, and its role for secondary brain damage, are still controversial. This review addresses recent clinical data on the influence of decompressive craniectomy on the brain pathophysiology in TBI. Decompressive craniectomy with dural augmentation enlarges intracranial space so that the swollen cerebral hemisphere could expand out of normal cranial limits, avoiding progression of brain herniation. The gain in intracranial volume results in both the improvement of cerebral compliance and a decrease in ICP; th...

Experimental physiology

The occurrence and implications of changes in cerebral autoregulation (CA) at high altitude are c... more The occurrence and implications of changes in cerebral autoregulation (CA) at high altitude are controversial and confounded by differences in methods used to assess CA. To compare two of the most common methods of dynamic CA assessment, we studied 11 young, healthy sea-level residents (6 female, 5 male; 20.5 ± 2.3 years) as they ascended and acclimatized to 3424 m over 13 days. A common autoregulation index (ARI) was calculated from 1) transfer function analysis (TFA ARI) of resting oscillations in arterial blood pressure (ABP; finger plethysmography) and middle cerebral artery blood velocity (MCAv; transcranial Doppler), and 2) MCAv responses following large, abrupt drops in ABP using the classic leg cuff technique (Cuff ARI). Symptoms of acute mountain sickness (AMS) were monitored using the Lake Louise AMS Questionnaire. Cuff ARI scores decreased (P = 0.021) as subjects ascended from low (4.7± 1.5) to high altitude (3.2 ± 1.6) and did not change after 13 days of acclimatization ...

Diabetes & vascular disease research, Jan 19, 2015

The aim of this study was to estimate the impact of diabetes and obesity on cerebral autoregulati... more The aim of this study was to estimate the impact of diabetes and obesity on cerebral autoregulation in pregnancy. Cerebral autoregulation was evaluated in women with gestational diabetes, type 2 diabetes mellitus and/or overweight (body mass index ⩾ 25 kg m(-2)) and compared to a cohort of euglycaemic pregnant women. The autoregulation index was calculated using simultaneously recorded cerebral blood flow velocity in the middle cerebral artery and blood pressure. Autoregulation index values of 0 and 9 indicate absent and perfect autoregulation, respectively. Autoregulation index in women with either diabetes (n = 33, 6.6 ± 1.1) or overweight (n = 21, 6.7 ± 0.6) was not significantly different to that in control patients (n = 23, 6.6 ± 0.8, p = 0.96). Cerebral autoregulation is not impaired in pregnant women who have non-vasculopathic diabetes or overweight. This suggests that the increased risk of pre-eclampsia in diabetic and overweight women is not associated with early impaired c...

Background and Purpose—Conventional methods of assessing cerebrovascular reactivity (CVR) omit th... more Background and Purpose—Conventional methods of assessing cerebrovascular reactivity (CVR) omit the influence of blood pressure (BP). This study demonstrates the significant influence of BP during the assessment of CVR in patients with carotid artery disease. Methods—In 56 subjects the CVR was bilaterally assessed by measurement of cerebral blood flow velocity change in response to inhalation of 5% CO2 in air

Journal of applied physiology (Bethesda, Md. : 1985), 2015

Preeclampsia (PE) is associated with endothelial dysfunction and impaired autonomic function, whi... more Preeclampsia (PE) is associated with endothelial dysfunction and impaired autonomic function, which is hypothesized to cause cerebral hemodynamic abnormalities. Our aim was to test this hypothesis by estimating the difference in the cerebrovascular response to breath holding (BH; known to cause sympathetic stimulation) between women with preeclampsia and a group of normotensive controls. In a prospective cohort analysis, cerebral blood flow velocity (CBFV) in the middle cerebral artery (transcranial Doppler), blood pressure (BP, noninvasive arterial volume clamping), and end-tidal carbon dioxide (EtCO2) were simultaneously recorded during a 20-s breath hold maneuver. CBFV changes were broken down into standardized subcomponents describing the relative contributions of BP, cerebrovascular resistance index (CVRi), critical closing pressure (CrCP), and resistance area product (RAP). The area under the curve (AUC) was calculated for changes in relation to baseline values. A total of 25 ...

Obstetrics and gynecology, 2013

To test the hypothesis that preeclampsia is associated with impaired dynamic cerebral autoregulat... more To test the hypothesis that preeclampsia is associated with impaired dynamic cerebral autoregulation. In a prospective cohort analysis, cerebral blood flow velocity of the middle cerebral artery (determined by transcranial Doppler), blood pressure (determined by noninvasive arterial volume clamping), and end-tidal carbon dioxide were simultaneously collected during a 7-minute period of rest. The autoregulation index was calculated. Values of 0 and 9 indicated absent and perfect autoregulation, respectively. Student t test was used, with P<.05 considered significant. Women with preeclampsia (before treatment, n=20) and their normotensive counterparts (n=20) did not differ with respect to baseline characteristics, except for earlier gestational age at delivery (36 3/7 [24 4/7-40 2/7] compared with 39 2/7 [32 0/7-41 0/7]; P<.001) and higher blood pressure in women with preeclampsia. Autoregulation index was significantly reduced in preeclamptic women compared with normotensive wo...

American journal of hypertension, 2003

Hypertension is known to increase the limits of static cerebral autoregulation (CA) but its effec... more Hypertension is known to increase the limits of static cerebral autoregulation (CA) but its effects on other aspects of CA such as efficiency and latency are unknown. In this study we test the hypothesis that dynamic cerebral autoregulation and the efficiency of static cerebral autoregulation are impaired by untreated hypertension. Cerebral blood flow velocity was recorded using transcranial Doppler ultrasound, along with noninvasive beat-to-beat blood pressure (BP), electrocardiogram, and transcutaneous carbon dioxide levels, with subjects at rest and during isometric hand grip, thigh cuff, and the Valsalva maneuver. Static and dynamic CA indices were calculated. No significant difference was seen in static or dynamic CA indices between normotensive and hypertensive groups for any pressor or depressor stimulus. Spearman's rank correlation showed no relation between static or dynamic CA indices and systemic BP levels for all maneuvers, but a significant relationship between age ...

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2013

In this work, we proposed a novel method to investigate the underlying rapid pressure-to-flow dyn... more In this work, we proposed a novel method to investigate the underlying rapid pressure-to-flow dynamics induced by changes of arterial CO2. Autoregulation was modeled as a multivariate system. The instantaneous effect of CO2 to cerebral blood flow velocity (CBFV) was removed adaptively by the recursive least square (RLS) method from CBFV. The residue CBFV and arterial blood pressure (ABP) were then filtered by a Gaussian-modulated sinusoidal pulse filter, in order to optimize the time and frequency resolution when estimating the instantaneous phase difference between the signals using Hilbert transform (HT). The results indicate that the effect of CO2 on dynamic autoregulation is slower than on CBFV.

Neuropediatrics, 1995

We have developed a method to estimate the critical closing pressure (CrCP) of the cerebral circu... more We have developed a method to estimate the critical closing pressure (CrCP) of the cerebral circulation based on the intrinsic variability of arterial blood pressure (BP) around stable values of mean arterial pressure (MAP). A consecutive cohort of 33 premature newborns was studied at 6, 12, 24, 48 and 72 hours of age. Cerebral blood flow velocity (CBFV) was measured with Doppler ultrasound in the middle cerebral artery and BP was recorded in the abdominal aorta or in a peripheral artery. Continuous measurements lasting five minutes were recorded on digital magnetic tape and signals were digitized at a rate of 200 samples/seconds for processing on a digital computer. Mean values of BP (mBP) and CBFV (mBV) were computed for each cardiac cycle and CrCP was determined as the pressure axis intercept of the regression line of mBV as a function of mBP using 100 sequential heart beats. The resistance-area product (RAP) was obtained from the slope of the regression line. For 57 records (30 patients) the mean +/- SD values of CrCP and RAP were 23.9 +/- 11.6 mmHg and 4.07 +/- 1.83 x 10(4) kg.m-2.s-1, respectively. CrCP has a highly significant correlation with mean arterial pressure (p &lt; 0.001) but RAP has not. Neither CrCP nor RAP are significantly correlated (p &gt; 0.05) with PO2, PCO2, pH, haematocrit, gestational age, birthweight, postnatal age, heart rate on Pourcelot&#39;s resistance index. Our results suggest that cerebral perfusion pressure should be defined as MAP-CrCP for normal values of intracranial pressure.

The dynamic relationship between spontaneous fluctuations of arterial blood pressure (ABP) and co... more The dynamic relationship between spontaneous fluctuations of arterial blood pressure (ABP) and corresponding changes in cerebral blood flow velocity (CBFV) is studied in a population of 83 neonates. Static and dynamic methods are used to identify two subgroups showing either normal (group A, n=23) or impaired (group B, n=21) cerebral autoregulation. An FFT algorithm is used to estimate the coherence and transfer function between CBFV and ABP. The significance of the linear dependence between these two variables is demonstrated by mean values of squared coherence >0.50 for both groups in the frequency range O.02-0.50 Hz. However, group A has significantly smaller coherences than group B in the frequency ranges O.02-0.10Hz and 0.33-0.49Hz. The phase response of group A is also significantly more positive than that of group B, with slopes of 9.34-1.05 and 1.804-1.2radHz-', respectively. The amplitude frequency response is also significantly smaller for group A in relation to group B for the frequency range 0.25--0.43 Hz. These results suggest that transfer function analysis may be able to identify different components of cerebral autoregulation and also provide a deeper understanding of recent findings by other investigators.

American journal of obstetrics and gynecology, Jan 7, 2014

Cerebrovascular complications that are associated with hypertensive disorders of pregnancy (preec... more Cerebrovascular complications that are associated with hypertensive disorders of pregnancy (preeclampsia, chronic hypertension [CHTN], and gestational hypertension [GHTN]) are believed to be associated with impaired cerebral autoregulation, which is a physiologic process that maintains blood flow at an appropriate level despite changes in blood pressure. The nature of autoregulation dysfunction in these conditions is unclear. We therefore evaluated autoregulation in 30 patients with preeclampsia, 30 patients with CHTN, and 20 patients with GHTN and compared them with a control group of 30 normal pregnant women. The autoregulatory index (ARI) was calculated with the use of simultaneously recorded cerebral blood flow velocity in the middle cerebral artery (transcranial Doppler ultrasound), blood pressure (noninvasive arterial volume clamping), and end-tidal carbon dioxide during a 7-minute period of rest. ARI values of 0 and 9 indicate absent and perfect autoregulation, respectively. ...

Cerebrovascular Diseases Extra, 2014

Acute stroke is known to impair cerebral blood flow (CBF) regulation, but the longitudinal change... more Acute stroke is known to impair cerebral blood flow (CBF) regulation, but the longitudinal changes of these effects have been poorly reported. The main CBF regulatory mechanisms [cerebral autoregulation (CA) and neurovascular coupling (NVC)] were assessed over 3 months after acute ischaemic stroke. Recordings of CBF velocity (CBFv), blood pressure (BP), and end-tidal CO2 were performed during 5 min baseline and 1 min passive movement of the elbow. Stroke patients were assessed &amp;amp;amp;amp;amp;amp;lt;72 h of stroke onset, and at 2 weeks, 1 and 3 months after stroke. Fifteen acute stroke subjects underwent all 4 sessions and were compared to 22 control subjects. Baseline recordings revealed a significantly lower CBFv in the affected hemisphere within 72 h after stroke compared to controls (p = 0.02) and a reduction in CA index most marked at 2 weeks (p = 0.009). CBFv rise in response to passive arm movement was decreased bilaterally after stroke, particularly in the affected hemisphere (p &amp;amp;amp;amp;amp;amp;lt; 0.01). Both alterations in CA and NVC returned to control levels during recovery. The major novel finding of this study was that both CA and NVC regulatory mechanisms deteriorated initially following stroke onset, but returned to control levels during the recovery period. These findings are relevant to guide the timing of interventions to manipulate BP and potentially for the impact of intensive rehabilitation strategies that may precipitate acute physiological perturbations but require further exploration in a larger population that better reflects the heterogeneity of stroke. Further, they will also enable the potential influence of stroke subtype to be investigated.

Perspectives in Medicine, 2012

Neurovascular coupling (NVC), analysed by a control system approach, was shown to be unaffected b... more Neurovascular coupling (NVC), analysed by a control system approach, was shown to be unaffected by orthostatic challenge, but data is lacking regarding the mechanism of this interplay and the behaviour of other cerebrovascular reactivity parameters. We investigated the changes in different pressure-velocity models during functional transcranial Doppler (TCD), under different orthostatic conditions.

Journal of applied physiology (Bethesda, Md. : 1985), 2014

The role of autonomic nervous system (ANS) in adapting cerebral blood flow (CBF) to arterial bloo... more The role of autonomic nervous system (ANS) in adapting cerebral blood flow (CBF) to arterial blood pressure (ABP) fluctuations [cerebral autoregulation (CA)] is still controversial. We aimed to study the repercussion of autonomic failure (AF) on dynamic CA during the Valsalva maneuver (VM). Eight AF subjects with familial amyloidotic polineuropahty (FAP) were compared with eight healthy controls. ABP and CBF velocity (CBFV) were measured continuously with Finapres and transcranial Doppler, respectively. Cerebrovascular response was evaluated by cerebrovascular resistance index (CVRi), critical closing pressure (CrCP), and resistance-area product (RAP) changes. Dynamic CA was derived from continuous estimates of autoregulatory index (ARI) [ARI(t)]. During phase II of VM, FAP subjects showed a more pronounced decrease in normalized CBFV (78 ± 19 and 111 ± 16%; P = 0.002), ABP (78 ± 19 and 124 ± 12%; P = 0.0003), and RAP (67 ± 17 and 89 ± 17%; P = 0.019) compared with controls. CrCP an...

Medical engineering & physics, 2014

Continuous assessment of CA is desirable in a number of clinical conditions, where cerebral hemod... more Continuous assessment of CA is desirable in a number of clinical conditions, where cerebral hemodynamics may change within relatively short periods. In this work, we propose a novel method that can improve temporal resolution when assessing the pressure-to-flow dynamics in the presence of rapid changes in arterial CO2. A time-varying multivariate model is proposed to adaptively suppress the instantaneous effect of CO2 on CBFV by the recursive least square (RLS) method. Autoregulation is then quantified from the phase difference (PD) between arterial blood pressure (ABP) and CBFV by calculating the instantaneous PD between the signals using the Hilbert transform (HT). A Gaussian filter is used prior to HT in order to optimize the temporal and frequency resolution and show the rapid dynamics of cerebral autoregulation. In 13 healthy adult volunteers, rapid changes of arterial CO2 were induced by rebreathing expired air, while simultaneously and continuously recording ABP, CBFV and end...

PLoS ONE, 2014

The classic dynamic autoregulatory index (ARI), proposed by Aaslid and Tiecks, is one of the most... more The classic dynamic autoregulatory index (ARI), proposed by Aaslid and Tiecks, is one of the most widely used methods to assess the efficiency of dynamic cerebral autoregulation. Although this index is often used in clinical research and is also included in some commercial equipment, it exhibits considerable intra-subject variability, and has the tendency to produce false positive results in clinical applications. An alternative index of dynamic cerebral autoregulation is proposed, which overcomes most of the limitations of the classic method and also has the advantage of being model-free. This new index uses two parameters that are obtained directly from the response signal of the cerebral blood flow velocity to a transient decrease in arterial blood pressure provoked by the sudden release of bilateral thigh cuffs, and a third parameter measuring the difference in slope of this response and the change in arterial blood pressure achieved. With the values of these parameters, a corresponding classic autoregulatory index value could be calculated by using a linear regression model built from theoretical curves generated with the Aaslid-Tiecks model. In 16 healthy subjects who underwent repeated thigh-cuff manoeuvres, the model-free approach exhibited significantly lower intra-subject variability, as measured by the unbiased coefficient of variation, than the classic autoregulatory index (p = 0.032) and the Rate of Return (p,0.001), another measure of cerebral autoregulation used for this type of systemic pressure stimulus, from 39.23%641.91% and 55.31%631.27%, respectively, to 15.98%67.75%.

Cardiovascular ultrasound, 2003

Studies suggest the physical and mechanical properties of vessel walls and plaque may be of clini... more Studies suggest the physical and mechanical properties of vessel walls and plaque may be of clinical value in the diagnosis and treatment of cardiovascular atherosclerotic disease. The purpose of this pilot study was to investigate the potential clinical application of ultrasound Tissue Doppler Imaging (TDI) of Arterial Wall Motion (AWM) and to quantify simple wall motion indices in normal and diseased carotid arteries. 224 normal and diseased carotid arteries (0-100% stenoses) were imaged in 126 patients (age 25-88 years, mean 68 +/- 11). Longitudinal sections of the carotid bifurcation were imaged using a Philips HDI5000 scanner and L12-5 probe under optimized TDI settings. Temporal and spatial AWMs were analyzed to evaluate the vessel wall displacements and spatial gradients at peak systole averaged over 5 cardiac cycles. AWM data were successfully extracted in 91% of cases. Within the carotid bifurcation/plaque region, the maximum wall dilation at peak systole ranged from -100 t...

Stroke, 2000

Background and Purpose-Dynamic methods of measuring cerebral autoregulation have become an accept... more Background and Purpose-Dynamic methods of measuring cerebral autoregulation have become an accepted alternative to static evaluation. This article aims to describe a set of data collected from healthy volunteers by a dynamic method, the purpose being to qualify and quantify expected results for those who may be designing a study using this technique. Methods-Cerebral blood flow velocity (CBFV) (measured by transcranial Doppler) and arterial blood pressure (Finapres) were recorded in 16 normal subjects before, during, and after the induction of a blood pressure drop (release of bilateral thigh cuffs). This procedure was repeated 6 times for each subject. A mathematical model was applied to the data to generate an autoregulatory index (ARI) with values between 0 and 9. Results-The ARI values for this sample population follow a normal distribution, with a meanϮSD of 4.98Ϯ1.06 (nϭ15).

Physiological Measurement, 1999

Arterial pCO2 is known to influence cerebral autoregulation but its effect on the dynamic relatio... more Arterial pCO2 is known to influence cerebral autoregulation but its effect on the dynamic relationship between mean arterial blood pressure (ABP) and mean cerebral blood flow velocity (CBFV), obtained from spontaneous fluctuations in ABP, has not been established. In 16 normal subjects, ABP was measured non-invasively (Finapres), CBFV was estimated with Doppler ultrasound in the middle cerebral artery, and end-tidal CO2 (EtCO2) was measured with an infrared capnograph. Recordings were made before, during and after breathing a mixture of 5% CO2 in air. The coherence function, amplitude and phase frequency responses, and impulse and step responses for the effects of ABP on CBFV were calculated by spectral analysis of beat-to-beat changes in mean ABP and CBFV before (mean CO2 5.55 +/- 0.38 kPa), during (6.43 +/- 0.31 kPa) and after 5% CO2 (5.43 +/- 0.26 kPa). During 5% CO2, the coherence function and the amplitude frequency response were significantly increased for frequencies below 0.05 Hz and the phase was reduced for the frequency range 0.02-0.1 Hz. The impulse and step responses indicated that 5% CO2 reduces the efficiency of the autoregulatory mechanism. A 20.7% average increase in CBFV induced by a 14.4% increase in EtCO2 was found to be mediated by a 25.9% reduction in critical closing pressure, while the change in resistance area product was non-significant.

Neurosurgical Review

There has been renewed interest in decompressive craniectomy as a surgical treatment for elevated... more There has been renewed interest in decompressive craniectomy as a surgical treatment for elevated intracranial pressure (ICP), although evidence-based clinical data are still lacking and some experimental results are conflicting. Ongoing clinical trials on the use of this operation after traumatic brain injury (TBI) may clarify the clinical application of this technique, however, some pathophysiological issues, such as the timing of this operation, its effect on brain edema formation, and its role for secondary brain damage, are still controversial. This review addresses recent clinical data on the influence of decompressive craniectomy on the brain pathophysiology in TBI. Decompressive craniectomy with dural augmentation enlarges intracranial space so that the swollen cerebral hemisphere could expand out of normal cranial limits, avoiding progression of brain herniation. The gain in intracranial volume results in both the improvement of cerebral compliance and a decrease in ICP; th...

Experimental physiology

The occurrence and implications of changes in cerebral autoregulation (CA) at high altitude are c... more The occurrence and implications of changes in cerebral autoregulation (CA) at high altitude are controversial and confounded by differences in methods used to assess CA. To compare two of the most common methods of dynamic CA assessment, we studied 11 young, healthy sea-level residents (6 female, 5 male; 20.5 ± 2.3 years) as they ascended and acclimatized to 3424 m over 13 days. A common autoregulation index (ARI) was calculated from 1) transfer function analysis (TFA ARI) of resting oscillations in arterial blood pressure (ABP; finger plethysmography) and middle cerebral artery blood velocity (MCAv; transcranial Doppler), and 2) MCAv responses following large, abrupt drops in ABP using the classic leg cuff technique (Cuff ARI). Symptoms of acute mountain sickness (AMS) were monitored using the Lake Louise AMS Questionnaire. Cuff ARI scores decreased (P = 0.021) as subjects ascended from low (4.7± 1.5) to high altitude (3.2 ± 1.6) and did not change after 13 days of acclimatization ...

Diabetes & vascular disease research, Jan 19, 2015

The aim of this study was to estimate the impact of diabetes and obesity on cerebral autoregulati... more The aim of this study was to estimate the impact of diabetes and obesity on cerebral autoregulation in pregnancy. Cerebral autoregulation was evaluated in women with gestational diabetes, type 2 diabetes mellitus and/or overweight (body mass index ⩾ 25 kg m(-2)) and compared to a cohort of euglycaemic pregnant women. The autoregulation index was calculated using simultaneously recorded cerebral blood flow velocity in the middle cerebral artery and blood pressure. Autoregulation index values of 0 and 9 indicate absent and perfect autoregulation, respectively. Autoregulation index in women with either diabetes (n = 33, 6.6 ± 1.1) or overweight (n = 21, 6.7 ± 0.6) was not significantly different to that in control patients (n = 23, 6.6 ± 0.8, p = 0.96). Cerebral autoregulation is not impaired in pregnant women who have non-vasculopathic diabetes or overweight. This suggests that the increased risk of pre-eclampsia in diabetic and overweight women is not associated with early impaired c...

Background and Purpose—Conventional methods of assessing cerebrovascular reactivity (CVR) omit th... more Background and Purpose—Conventional methods of assessing cerebrovascular reactivity (CVR) omit the influence of blood pressure (BP). This study demonstrates the significant influence of BP during the assessment of CVR in patients with carotid artery disease. Methods—In 56 subjects the CVR was bilaterally assessed by measurement of cerebral blood flow velocity change in response to inhalation of 5% CO2 in air

Journal of applied physiology (Bethesda, Md. : 1985), 2015

Preeclampsia (PE) is associated with endothelial dysfunction and impaired autonomic function, whi... more Preeclampsia (PE) is associated with endothelial dysfunction and impaired autonomic function, which is hypothesized to cause cerebral hemodynamic abnormalities. Our aim was to test this hypothesis by estimating the difference in the cerebrovascular response to breath holding (BH; known to cause sympathetic stimulation) between women with preeclampsia and a group of normotensive controls. In a prospective cohort analysis, cerebral blood flow velocity (CBFV) in the middle cerebral artery (transcranial Doppler), blood pressure (BP, noninvasive arterial volume clamping), and end-tidal carbon dioxide (EtCO2) were simultaneously recorded during a 20-s breath hold maneuver. CBFV changes were broken down into standardized subcomponents describing the relative contributions of BP, cerebrovascular resistance index (CVRi), critical closing pressure (CrCP), and resistance area product (RAP). The area under the curve (AUC) was calculated for changes in relation to baseline values. A total of 25 ...

Obstetrics and gynecology, 2013

To test the hypothesis that preeclampsia is associated with impaired dynamic cerebral autoregulat... more To test the hypothesis that preeclampsia is associated with impaired dynamic cerebral autoregulation. In a prospective cohort analysis, cerebral blood flow velocity of the middle cerebral artery (determined by transcranial Doppler), blood pressure (determined by noninvasive arterial volume clamping), and end-tidal carbon dioxide were simultaneously collected during a 7-minute period of rest. The autoregulation index was calculated. Values of 0 and 9 indicated absent and perfect autoregulation, respectively. Student t test was used, with P<.05 considered significant. Women with preeclampsia (before treatment, n=20) and their normotensive counterparts (n=20) did not differ with respect to baseline characteristics, except for earlier gestational age at delivery (36 3/7 [24 4/7-40 2/7] compared with 39 2/7 [32 0/7-41 0/7]; P<.001) and higher blood pressure in women with preeclampsia. Autoregulation index was significantly reduced in preeclamptic women compared with normotensive wo...

American journal of hypertension, 2003

Hypertension is known to increase the limits of static cerebral autoregulation (CA) but its effec... more Hypertension is known to increase the limits of static cerebral autoregulation (CA) but its effects on other aspects of CA such as efficiency and latency are unknown. In this study we test the hypothesis that dynamic cerebral autoregulation and the efficiency of static cerebral autoregulation are impaired by untreated hypertension. Cerebral blood flow velocity was recorded using transcranial Doppler ultrasound, along with noninvasive beat-to-beat blood pressure (BP), electrocardiogram, and transcutaneous carbon dioxide levels, with subjects at rest and during isometric hand grip, thigh cuff, and the Valsalva maneuver. Static and dynamic CA indices were calculated. No significant difference was seen in static or dynamic CA indices between normotensive and hypertensive groups for any pressor or depressor stimulus. Spearman's rank correlation showed no relation between static or dynamic CA indices and systemic BP levels for all maneuvers, but a significant relationship between age ...

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2013

In this work, we proposed a novel method to investigate the underlying rapid pressure-to-flow dyn... more In this work, we proposed a novel method to investigate the underlying rapid pressure-to-flow dynamics induced by changes of arterial CO2. Autoregulation was modeled as a multivariate system. The instantaneous effect of CO2 to cerebral blood flow velocity (CBFV) was removed adaptively by the recursive least square (RLS) method from CBFV. The residue CBFV and arterial blood pressure (ABP) were then filtered by a Gaussian-modulated sinusoidal pulse filter, in order to optimize the time and frequency resolution when estimating the instantaneous phase difference between the signals using Hilbert transform (HT). The results indicate that the effect of CO2 on dynamic autoregulation is slower than on CBFV.

Neuropediatrics, 1995

We have developed a method to estimate the critical closing pressure (CrCP) of the cerebral circu... more We have developed a method to estimate the critical closing pressure (CrCP) of the cerebral circulation based on the intrinsic variability of arterial blood pressure (BP) around stable values of mean arterial pressure (MAP). A consecutive cohort of 33 premature newborns was studied at 6, 12, 24, 48 and 72 hours of age. Cerebral blood flow velocity (CBFV) was measured with Doppler ultrasound in the middle cerebral artery and BP was recorded in the abdominal aorta or in a peripheral artery. Continuous measurements lasting five minutes were recorded on digital magnetic tape and signals were digitized at a rate of 200 samples/seconds for processing on a digital computer. Mean values of BP (mBP) and CBFV (mBV) were computed for each cardiac cycle and CrCP was determined as the pressure axis intercept of the regression line of mBV as a function of mBP using 100 sequential heart beats. The resistance-area product (RAP) was obtained from the slope of the regression line. For 57 records (30 patients) the mean +/- SD values of CrCP and RAP were 23.9 +/- 11.6 mmHg and 4.07 +/- 1.83 x 10(4) kg.m-2.s-1, respectively. CrCP has a highly significant correlation with mean arterial pressure (p &lt; 0.001) but RAP has not. Neither CrCP nor RAP are significantly correlated (p &gt; 0.05) with PO2, PCO2, pH, haematocrit, gestational age, birthweight, postnatal age, heart rate on Pourcelot&#39;s resistance index. Our results suggest that cerebral perfusion pressure should be defined as MAP-CrCP for normal values of intracranial pressure.

The dynamic relationship between spontaneous fluctuations of arterial blood pressure (ABP) and co... more The dynamic relationship between spontaneous fluctuations of arterial blood pressure (ABP) and corresponding changes in cerebral blood flow velocity (CBFV) is studied in a population of 83 neonates. Static and dynamic methods are used to identify two subgroups showing either normal (group A, n=23) or impaired (group B, n=21) cerebral autoregulation. An FFT algorithm is used to estimate the coherence and transfer function between CBFV and ABP. The significance of the linear dependence between these two variables is demonstrated by mean values of squared coherence >0.50 for both groups in the frequency range O.02-0.50 Hz. However, group A has significantly smaller coherences than group B in the frequency ranges O.02-0.10Hz and 0.33-0.49Hz. The phase response of group A is also significantly more positive than that of group B, with slopes of 9.34-1.05 and 1.804-1.2radHz-', respectively. The amplitude frequency response is also significantly smaller for group A in relation to group B for the frequency range 0.25--0.43 Hz. These results suggest that transfer function analysis may be able to identify different components of cerebral autoregulation and also provide a deeper understanding of recent findings by other investigators.

American journal of obstetrics and gynecology, Jan 7, 2014

Cerebrovascular complications that are associated with hypertensive disorders of pregnancy (preec... more Cerebrovascular complications that are associated with hypertensive disorders of pregnancy (preeclampsia, chronic hypertension [CHTN], and gestational hypertension [GHTN]) are believed to be associated with impaired cerebral autoregulation, which is a physiologic process that maintains blood flow at an appropriate level despite changes in blood pressure. The nature of autoregulation dysfunction in these conditions is unclear. We therefore evaluated autoregulation in 30 patients with preeclampsia, 30 patients with CHTN, and 20 patients with GHTN and compared them with a control group of 30 normal pregnant women. The autoregulatory index (ARI) was calculated with the use of simultaneously recorded cerebral blood flow velocity in the middle cerebral artery (transcranial Doppler ultrasound), blood pressure (noninvasive arterial volume clamping), and end-tidal carbon dioxide during a 7-minute period of rest. ARI values of 0 and 9 indicate absent and perfect autoregulation, respectively. ...

Cerebrovascular Diseases Extra, 2014

Acute stroke is known to impair cerebral blood flow (CBF) regulation, but the longitudinal change... more Acute stroke is known to impair cerebral blood flow (CBF) regulation, but the longitudinal changes of these effects have been poorly reported. The main CBF regulatory mechanisms [cerebral autoregulation (CA) and neurovascular coupling (NVC)] were assessed over 3 months after acute ischaemic stroke. Recordings of CBF velocity (CBFv), blood pressure (BP), and end-tidal CO2 were performed during 5 min baseline and 1 min passive movement of the elbow. Stroke patients were assessed &amp;amp;amp;amp;amp;amp;lt;72 h of stroke onset, and at 2 weeks, 1 and 3 months after stroke. Fifteen acute stroke subjects underwent all 4 sessions and were compared to 22 control subjects. Baseline recordings revealed a significantly lower CBFv in the affected hemisphere within 72 h after stroke compared to controls (p = 0.02) and a reduction in CA index most marked at 2 weeks (p = 0.009). CBFv rise in response to passive arm movement was decreased bilaterally after stroke, particularly in the affected hemisphere (p &amp;amp;amp;amp;amp;amp;lt; 0.01). Both alterations in CA and NVC returned to control levels during recovery. The major novel finding of this study was that both CA and NVC regulatory mechanisms deteriorated initially following stroke onset, but returned to control levels during the recovery period. These findings are relevant to guide the timing of interventions to manipulate BP and potentially for the impact of intensive rehabilitation strategies that may precipitate acute physiological perturbations but require further exploration in a larger population that better reflects the heterogeneity of stroke. Further, they will also enable the potential influence of stroke subtype to be investigated.

Perspectives in Medicine, 2012

Neurovascular coupling (NVC), analysed by a control system approach, was shown to be unaffected b... more Neurovascular coupling (NVC), analysed by a control system approach, was shown to be unaffected by orthostatic challenge, but data is lacking regarding the mechanism of this interplay and the behaviour of other cerebrovascular reactivity parameters. We investigated the changes in different pressure-velocity models during functional transcranial Doppler (TCD), under different orthostatic conditions.

Journal of applied physiology (Bethesda, Md. : 1985), 2014

The role of autonomic nervous system (ANS) in adapting cerebral blood flow (CBF) to arterial bloo... more The role of autonomic nervous system (ANS) in adapting cerebral blood flow (CBF) to arterial blood pressure (ABP) fluctuations [cerebral autoregulation (CA)] is still controversial. We aimed to study the repercussion of autonomic failure (AF) on dynamic CA during the Valsalva maneuver (VM). Eight AF subjects with familial amyloidotic polineuropahty (FAP) were compared with eight healthy controls. ABP and CBF velocity (CBFV) were measured continuously with Finapres and transcranial Doppler, respectively. Cerebrovascular response was evaluated by cerebrovascular resistance index (CVRi), critical closing pressure (CrCP), and resistance-area product (RAP) changes. Dynamic CA was derived from continuous estimates of autoregulatory index (ARI) [ARI(t)]. During phase II of VM, FAP subjects showed a more pronounced decrease in normalized CBFV (78 ± 19 and 111 ± 16%; P = 0.002), ABP (78 ± 19 and 124 ± 12%; P = 0.0003), and RAP (67 ± 17 and 89 ± 17%; P = 0.019) compared with controls. CrCP an...

Medical engineering & physics, 2014

Continuous assessment of CA is desirable in a number of clinical conditions, where cerebral hemod... more Continuous assessment of CA is desirable in a number of clinical conditions, where cerebral hemodynamics may change within relatively short periods. In this work, we propose a novel method that can improve temporal resolution when assessing the pressure-to-flow dynamics in the presence of rapid changes in arterial CO2. A time-varying multivariate model is proposed to adaptively suppress the instantaneous effect of CO2 on CBFV by the recursive least square (RLS) method. Autoregulation is then quantified from the phase difference (PD) between arterial blood pressure (ABP) and CBFV by calculating the instantaneous PD between the signals using the Hilbert transform (HT). A Gaussian filter is used prior to HT in order to optimize the temporal and frequency resolution and show the rapid dynamics of cerebral autoregulation. In 13 healthy adult volunteers, rapid changes of arterial CO2 were induced by rebreathing expired air, while simultaneously and continuously recording ABP, CBFV and end...

PLoS ONE, 2014

The classic dynamic autoregulatory index (ARI), proposed by Aaslid and Tiecks, is one of the most... more The classic dynamic autoregulatory index (ARI), proposed by Aaslid and Tiecks, is one of the most widely used methods to assess the efficiency of dynamic cerebral autoregulation. Although this index is often used in clinical research and is also included in some commercial equipment, it exhibits considerable intra-subject variability, and has the tendency to produce false positive results in clinical applications. An alternative index of dynamic cerebral autoregulation is proposed, which overcomes most of the limitations of the classic method and also has the advantage of being model-free. This new index uses two parameters that are obtained directly from the response signal of the cerebral blood flow velocity to a transient decrease in arterial blood pressure provoked by the sudden release of bilateral thigh cuffs, and a third parameter measuring the difference in slope of this response and the change in arterial blood pressure achieved. With the values of these parameters, a corresponding classic autoregulatory index value could be calculated by using a linear regression model built from theoretical curves generated with the Aaslid-Tiecks model. In 16 healthy subjects who underwent repeated thigh-cuff manoeuvres, the model-free approach exhibited significantly lower intra-subject variability, as measured by the unbiased coefficient of variation, than the classic autoregulatory index (p = 0.032) and the Rate of Return (p,0.001), another measure of cerebral autoregulation used for this type of systemic pressure stimulus, from 39.23%641.91% and 55.31%631.27%, respectively, to 15.98%67.75%.

Cardiovascular ultrasound, 2003

Studies suggest the physical and mechanical properties of vessel walls and plaque may be of clini... more Studies suggest the physical and mechanical properties of vessel walls and plaque may be of clinical value in the diagnosis and treatment of cardiovascular atherosclerotic disease. The purpose of this pilot study was to investigate the potential clinical application of ultrasound Tissue Doppler Imaging (TDI) of Arterial Wall Motion (AWM) and to quantify simple wall motion indices in normal and diseased carotid arteries. 224 normal and diseased carotid arteries (0-100% stenoses) were imaged in 126 patients (age 25-88 years, mean 68 +/- 11). Longitudinal sections of the carotid bifurcation were imaged using a Philips HDI5000 scanner and L12-5 probe under optimized TDI settings. Temporal and spatial AWMs were analyzed to evaluate the vessel wall displacements and spatial gradients at peak systole averaged over 5 cardiac cycles. AWM data were successfully extracted in 91% of cases. Within the carotid bifurcation/plaque region, the maximum wall dilation at peak systole ranged from -100 t...

Stroke, 2000

Background and Purpose-Dynamic methods of measuring cerebral autoregulation have become an accept... more Background and Purpose-Dynamic methods of measuring cerebral autoregulation have become an accepted alternative to static evaluation. This article aims to describe a set of data collected from healthy volunteers by a dynamic method, the purpose being to qualify and quantify expected results for those who may be designing a study using this technique. Methods-Cerebral blood flow velocity (CBFV) (measured by transcranial Doppler) and arterial blood pressure (Finapres) were recorded in 16 normal subjects before, during, and after the induction of a blood pressure drop (release of bilateral thigh cuffs). This procedure was repeated 6 times for each subject. A mathematical model was applied to the data to generate an autoregulatory index (ARI) with values between 0 and 9. Results-The ARI values for this sample population follow a normal distribution, with a meanϮSD of 4.98Ϯ1.06 (nϭ15).

Physiological Measurement, 1999

Arterial pCO2 is known to influence cerebral autoregulation but its effect on the dynamic relatio... more Arterial pCO2 is known to influence cerebral autoregulation but its effect on the dynamic relationship between mean arterial blood pressure (ABP) and mean cerebral blood flow velocity (CBFV), obtained from spontaneous fluctuations in ABP, has not been established. In 16 normal subjects, ABP was measured non-invasively (Finapres), CBFV was estimated with Doppler ultrasound in the middle cerebral artery, and end-tidal CO2 (EtCO2) was measured with an infrared capnograph. Recordings were made before, during and after breathing a mixture of 5% CO2 in air. The coherence function, amplitude and phase frequency responses, and impulse and step responses for the effects of ABP on CBFV were calculated by spectral analysis of beat-to-beat changes in mean ABP and CBFV before (mean CO2 5.55 +/- 0.38 kPa), during (6.43 +/- 0.31 kPa) and after 5% CO2 (5.43 +/- 0.26 kPa). During 5% CO2, the coherence function and the amplitude frequency response were significantly increased for frequencies below 0.05 Hz and the phase was reduced for the frequency range 0.02-0.1 Hz. The impulse and step responses indicated that 5% CO2 reduces the efficiency of the autoregulatory mechanism. A 20.7% average increase in CBFV induced by a 14.4% increase in EtCO2 was found to be mediated by a 25.9% reduction in critical closing pressure, while the change in resistance area product was non-significant.