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I V pertensione Intracranica: alutazione con TCD Dr. Frank Rasulo

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1 I V pertensione Intracranica: alutazione con TCD Dr. Frank Rasulo
LA NEUROSONOLOGIA NELL’AMBITO DELLE NEUROSCIENZE: Primo Corso teorico pratico BRESCIA 12-13 NOVEMBRE 2010 U.O. Neurorianimazione Spedali Civili di Brescia I pertensione Intracranica: V alutazione con TCD Dr. Frank Rasulo U.O. Neurorianimazione Università di Brescia

2 TCD in the ICU SUBARACHNOID HEMORRHAGE HEAD TRAUMA STROKE BRAIN DEATH
VASOSPASM INTRACRANIAL HYPERTENSION CEREBRAL CIRCULATORY ARREST AUTOREGULATION STENOSIS SUBARACHNOID HEMORRHAGE HEAD TRAUMA STROKE BRAIN DEATH SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

3 d iagnosing high ICP The gold standard for the measurement of
ICP is its invasive measurement. SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

4 T ypes of Devices TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA
SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

5 on invasive evaluation of high ICP
However there are various situations where a non invasive measurement may be useful… mild and moderate head injury Ischemic & hemorrhagic stroke, vasospasm meningo-encephalytis faulty ICP cathters outside the ICU (ER, OR, etc.) SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

6 CD waveform analysis for the evaluation of intracranial pressure
SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

7 TCD -derived parameters Mean flow velocity
partial information regarding cerebral hemodynamics, not optimal to assess biophysical properties of the brain. Systolic flow velocity FV systolic is predominantly dependant on the cardiac output systemic hemodynamics, rather than depicting cerebral hemodynamics. Mean flow velocity FV is proportional to the cerebral blood flow (CBF) under normal conditions. This proportionality is dependent on numerous factors, especially the cross-sectional area of the insonated artery and the cosine of the angle of insonation (i.e. the angle between the direction of flow and the ultrasonic beam). Although TCD is not appropriate to yield an absolute value of CBF, changes over time in FV are related to changes in CBF [Bishop 1986, Dahl 1992]. Therefore, TCD gives a semi-quantitative measurement of FV, and changes in FV provide a quantitative measurement of changes in CBF. Hence FV mean give partial information on cerebral haemodynamics, and is not optimal to assess biophysical properties of the brain. Systolic flow velocity FV systolic is predominantly dependant on the cardiac output i.e. systemic haemodynamics, rather than depicting cerebral haemodynamics. Diastolic flow velocity Albeit a sparse literature, the use of diastolic FV as a relevant parameter is currently thriving in clinical practice, especially in intensive care. One clinical research report that a reduction of CPP by rising ICP or by falling BP in head injured patients, resulted in a greater fall in diastolic flow velocity than other flow parameters [Chan 1992]. As well, in a pediatric head trauma study, an end-diastolic velocity less than 25 cm/s was associated with a poor prognosis [Trabold 2004]. At least, one animal experiment reported the disappearance of FV diastolic to be correlated with the drop of CBF [Nagai 1997]. FV diastolic remains an interesting but ill-defined parameter. Its pathophysiological significance remains to be elucidated. Clear thresholds for FV diastolic and its clinical relevance have to be published. Pulsatility index The reports on the use of pulsatility index (PI) in assessing ICP are conflicting. Few studies demonstrated a poor correlation between PI and ICP [Hanlo 1995, Harada 1993], others a highly significant correlation between those two variables [Bellner 2004, Voulgaris 2005]. But the value of FV (high or low) seems to influence the correlation between PI and ICP [Bellner 2004]. More recently, in pediatric head injury, a pulsatility index higher than 1.31 has been demonstrated to be associated with a poor prognosis [Trabold 2004]. Interestingly PI also strongly correlates with CPP [Chan 1992, Bellner 2004, Voulgaris 2005], but the relationship is the same whether changes in CPP resulted from changes in ICP or ABP [Chan 1992]. The influence of systemic haemodynamics on PI, that is upstream forces, has also been demonstrated [Evans 1980, Rossitti 1995, Gooskens 2003]. At least, experimental data demonstrated that PI is in fact dependant on ICP, on ABP, consequently on CPP and on vascular tone (CO2) [Czosnyka 1996]. To summarize, changes in PI are correlated to both changes in ICP and ABP. Although few papers favour PI as a surrogate ICP, the sensitivity of PI to identify raised ICP is high, but its specificity is low. Diastolic flow velocity Pulsatility index SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

8 TCD -derived parameters Mean flow velocity
partial information regarding cerebral hemodynamics, not optimal to assess biophysical properties of the brain. Systolic flow velocity FV systolic is predominantly dependant on the cardiac output systemic hemodynamics, rather than depicting cerebral hemodynamics. Mean flow velocity FV is proportional to the cerebral blood flow (CBF) under normal conditions. This proportionality is dependent on numerous factors, especially the cross-sectional area of the insonated artery and the cosine of the angle of insonation (i.e. the angle between the direction of flow and the ultrasonic beam). Although TCD is not appropriate to yield an absolute value of CBF, changes over time in FV are related to changes in CBF [Bishop 1986, Dahl 1992]. Therefore, TCD gives a semi-quantitative measurement of FV, and changes in FV provide a quantitative measurement of changes in CBF. Hence FV mean give partial information on cerebral haemodynamics, and is not optimal to assess biophysical properties of the brain. Systolic flow velocity FV systolic is predominantly dependant on the cardiac output i.e. systemic haemodynamics, rather than depicting cerebral haemodynamics. Diastolic flow velocity Albeit a sparse literature, the use of diastolic FV as a relevant parameter is currently thriving in clinical practice, especially in intensive care. One clinical research report that a reduction of CPP by rising ICP or by falling BP in head injured patients, resulted in a greater fall in diastolic flow velocity than other flow parameters [Chan 1992]. As well, in a pediatric head trauma study, an end-diastolic velocity less than 25 cm/s was associated with a poor prognosis [Trabold 2004]. At least, one animal experiment reported the disappearance of FV diastolic to be correlated with the drop of CBF [Nagai 1997]. FV diastolic remains an interesting but ill-defined parameter. Its pathophysiological significance remains to be elucidated. Clear thresholds for FV diastolic and its clinical relevance have to be published. Pulsatility index The reports on the use of pulsatility index (PI) in assessing ICP are conflicting. Few studies demonstrated a poor correlation between PI and ICP [Hanlo 1995, Harada 1993], others a highly significant correlation between those two variables [Bellner 2004, Voulgaris 2005]. But the value of FV (high or low) seems to influence the correlation between PI and ICP [Bellner 2004]. More recently, in pediatric head injury, a pulsatility index higher than 1.31 has been demonstrated to be associated with a poor prognosis [Trabold 2004]. Interestingly PI also strongly correlates with CPP [Chan 1992, Bellner 2004, Voulgaris 2005], but the relationship is the same whether changes in CPP resulted from changes in ICP or ABP [Chan 1992]. The influence of systemic haemodynamics on PI, that is upstream forces, has also been demonstrated [Evans 1980, Rossitti 1995, Gooskens 2003]. At least, experimental data demonstrated that PI is in fact dependant on ICP, on ABP, consequently on CPP and on vascular tone (CO2) [Czosnyka 1996]. To summarize, changes in PI are correlated to both changes in ICP and ABP. Although few papers favour PI as a surrogate ICP, the sensitivity of PI to identify raised ICP is high, but its specificity is low. Diastolic flow velocity Pulsatility index SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

9 TCD -derived parameters Mean flow velocity
partial information regarding cerebral hemodynamics, not optimal to assess biophysical properties of the brain. Systolic flow velocity FV systolic is predominantly dependant on the cardiac output systemic hemodynamics, rather than depicting cerebral hemodynamics. Mean flow velocity FV is proportional to the cerebral blood flow (CBF) under normal conditions. This proportionality is dependent on numerous factors, especially the cross-sectional area of the insonated artery and the cosine of the angle of insonation (i.e. the angle between the direction of flow and the ultrasonic beam). Although TCD is not appropriate to yield an absolute value of CBF, changes over time in FV are related to changes in CBF [Bishop 1986, Dahl 1992]. Therefore, TCD gives a semi-quantitative measurement of FV, and changes in FV provide a quantitative measurement of changes in CBF. Hence FV mean give partial information on cerebral haemodynamics, and is not optimal to assess biophysical properties of the brain. Systolic flow velocity FV systolic is predominantly dependant on the cardiac output i.e. systemic haemodynamics, rather than depicting cerebral haemodynamics. Diastolic flow velocity Albeit a sparse literature, the use of diastolic FV as a relevant parameter is currently thriving in clinical practice, especially in intensive care. One clinical research report that a reduction of CPP by rising ICP or by falling BP in head injured patients, resulted in a greater fall in diastolic flow velocity than other flow parameters [Chan 1992]. As well, in a pediatric head trauma study, an end-diastolic velocity less than 25 cm/s was associated with a poor prognosis [Trabold 2004]. At least, one animal experiment reported the disappearance of FV diastolic to be correlated with the drop of CBF [Nagai 1997]. FV diastolic remains an interesting but ill-defined parameter. Its pathophysiological significance remains to be elucidated. Clear thresholds for FV diastolic and its clinical relevance have to be published. Pulsatility index The reports on the use of pulsatility index (PI) in assessing ICP are conflicting. Few studies demonstrated a poor correlation between PI and ICP [Hanlo 1995, Harada 1993], others a highly significant correlation between those two variables [Bellner 2004, Voulgaris 2005]. But the value of FV (high or low) seems to influence the correlation between PI and ICP [Bellner 2004]. More recently, in pediatric head injury, a pulsatility index higher than 1.31 has been demonstrated to be associated with a poor prognosis [Trabold 2004]. Interestingly PI also strongly correlates with CPP [Chan 1992, Bellner 2004, Voulgaris 2005], but the relationship is the same whether changes in CPP resulted from changes in ICP or ABP [Chan 1992]. The influence of systemic haemodynamics on PI, that is upstream forces, has also been demonstrated [Evans 1980, Rossitti 1995, Gooskens 2003]. At least, experimental data demonstrated that PI is in fact dependant on ICP, on ABP, consequently on CPP and on vascular tone (CO2) [Czosnyka 1996]. To summarize, changes in PI are correlated to both changes in ICP and ABP. Although few papers favour PI as a surrogate ICP, the sensitivity of PI to identify raised ICP is high, but its specificity is low. Diastolic flow velocity Pulsatility index SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

10 TCD -derived parameters Mean flow velocity
partial information regarding cerebral hemodynamics, not optimal to assess biophysical properties of the brain. Systolic flow velocity FV systolic is predominantly dependant on the cardiac output systemic hemodynamics, rather than depicting cerebral hemodynamics. Mean flow velocity FV is proportional to the cerebral blood flow (CBF) under normal conditions. This proportionality is dependent on numerous factors, especially the cross-sectional area of the insonated artery and the cosine of the angle of insonation (i.e. the angle between the direction of flow and the ultrasonic beam). Although TCD is not appropriate to yield an absolute value of CBF, changes over time in FV are related to changes in CBF [Bishop 1986, Dahl 1992]. Therefore, TCD gives a semi-quantitative measurement of FV, and changes in FV provide a quantitative measurement of changes in CBF. Hence FV mean give partial information on cerebral haemodynamics, and is not optimal to assess biophysical properties of the brain. Systolic flow velocity FV systolic is predominantly dependant on the cardiac output i.e. systemic haemodynamics, rather than depicting cerebral haemodynamics. Diastolic flow velocity Albeit a sparse literature, the use of diastolic FV as a relevant parameter is currently thriving in clinical practice, especially in intensive care. One clinical research report that a reduction of CPP by rising ICP or by falling BP in head injured patients, resulted in a greater fall in diastolic flow velocity than other flow parameters [Chan 1992]. As well, in a pediatric head trauma study, an end-diastolic velocity less than 25 cm/s was associated with a poor prognosis [Trabold 2004]. At least, one animal experiment reported the disappearance of FV diastolic to be correlated with the drop of CBF [Nagai 1997]. FV diastolic remains an interesting but ill-defined parameter. Its pathophysiological significance remains to be elucidated. Clear thresholds for FV diastolic and its clinical relevance have to be published. Pulsatility index The reports on the use of pulsatility index (PI) in assessing ICP are conflicting. Few studies demonstrated a poor correlation between PI and ICP [Hanlo 1995, Harada 1993], others a highly significant correlation between those two variables [Bellner 2004, Voulgaris 2005]. But the value of FV (high or low) seems to influence the correlation between PI and ICP [Bellner 2004]. More recently, in pediatric head injury, a pulsatility index higher than 1.31 has been demonstrated to be associated with a poor prognosis [Trabold 2004]. Interestingly PI also strongly correlates with CPP [Chan 1992, Bellner 2004, Voulgaris 2005], but the relationship is the same whether changes in CPP resulted from changes in ICP or ABP [Chan 1992]. The influence of systemic haemodynamics on PI, that is upstream forces, has also been demonstrated [Evans 1980, Rossitti 1995, Gooskens 2003]. At least, experimental data demonstrated that PI is in fact dependant on ICP, on ABP, consequently on CPP and on vascular tone (CO2) [Czosnyka 1996]. To summarize, changes in PI are correlated to both changes in ICP and ABP. Although few papers favour PI as a surrogate ICP, the sensitivity of PI to identify raised ICP is high, but its specificity is low. Diastolic flow velocity Pulsatility index SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

11 CD for non invasive ICP EVALUATION
SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

12 CD for non invasive ICP EVALUATION
SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

13 TCD -derived parameters Diastolic flow velocity
Chan KH. The effect of changes in cerebral perfusion pressure upon middle cerebral artery blood flow velocity and jugular bulb venous oxygen saturation after severe brain injury. J Neurosurg Jul;77(1):55-61. “a reduction of CPP by rising ICP or by falling BP in head injured patients, resulted in a greater fall in diastolic flow velocity than other flow parameters” Trabold F. The prognostic value of transcranial Doppler studies in children with moderate and severe head injury. Intensive Care Med. 2004;30(1):108-12 Pediatric head trauma study, an end-diastolic velocity less than 25 cm/s was associated with a poor prognosis SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

14 CD for non invasive ICP EVALUATION
Monitorare il ritardo di crescita: la flussimetria dell'arteria ombelicale  Il flusso diastolico normale in un feto Il flusso diastolico assente richiede invece la valutazione di altri distretti fetali quali l'arteria cerebrale media ed il dotto venoso, due vasi che danno informazioni sul benessere fetale,  Il flusso diastolico invertito rappresenta una condizione particolarmente a rischio e come tale deve essere gestita. Monitorare il ritardo di crescita: la flussimetria dell'arteria ombelicaleLaflussimetria dell'arteria ombelicale rappresenta lo strumento più efficace per individuare tra i feti con ritardo di crescita quelli a maggior rischio di sviluppare ipossia (=ridotto apporto di ossigeno).Anche per l'arteria ombelicale, come per le arterie uterine, si valutano degli indici flussimetrici detti P.I. e R.I.: il flusso nell'arteria ombelicale è correlato al corretto sviluppo placentare sul versante fetale, cioè ci dice come funziona la placenta. Per fare un esempio, è come il contatore della benzina: la flussimetria dell'arteria ombelicale ci dà un'idea di quanta "benzina" abbiamo e di quanto possiamo andare lontano con sicurezza. SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

15 TCD -derived parameters Mean flow velocity
partial information regarding cerebral hemodynamics, not optimal to assess biophysical properties of the brain. Systolic flow velocity FV systolic is predominantly dependant on the cardiac output systemic hemodynamics, rather than depicting cerebral hemodynamics. Mean flow velocity FV is proportional to the cerebral blood flow (CBF) under normal conditions. This proportionality is dependent on numerous factors, especially the cross-sectional area of the insonated artery and the cosine of the angle of insonation (i.e. the angle between the direction of flow and the ultrasonic beam). Although TCD is not appropriate to yield an absolute value of CBF, changes over time in FV are related to changes in CBF [Bishop 1986, Dahl 1992]. Therefore, TCD gives a semi-quantitative measurement of FV, and changes in FV provide a quantitative measurement of changes in CBF. Hence FV mean give partial information on cerebral haemodynamics, and is not optimal to assess biophysical properties of the brain. Systolic flow velocity FV systolic is predominantly dependant on the cardiac output i.e. systemic haemodynamics, rather than depicting cerebral haemodynamics. Diastolic flow velocity Albeit a sparse literature, the use of diastolic FV as a relevant parameter is currently thriving in clinical practice, especially in intensive care. One clinical research report that a reduction of CPP by rising ICP or by falling BP in head injured patients, resulted in a greater fall in diastolic flow velocity than other flow parameters [Chan 1992]. As well, in a pediatric head trauma study, an end-diastolic velocity less than 25 cm/s was associated with a poor prognosis [Trabold 2004]. At least, one animal experiment reported the disappearance of FV diastolic to be correlated with the drop of CBF [Nagai 1997]. FV diastolic remains an interesting but ill-defined parameter. Its pathophysiological significance remains to be elucidated. Clear thresholds for FV diastolic and its clinical relevance have to be published. Pulsatility index The reports on the use of pulsatility index (PI) in assessing ICP are conflicting. Few studies demonstrated a poor correlation between PI and ICP [Hanlo 1995, Harada 1993], others a highly significant correlation between those two variables [Bellner 2004, Voulgaris 2005]. But the value of FV (high or low) seems to influence the correlation between PI and ICP [Bellner 2004]. More recently, in pediatric head injury, a pulsatility index higher than 1.31 has been demonstrated to be associated with a poor prognosis [Trabold 2004]. Interestingly PI also strongly correlates with CPP [Chan 1992, Bellner 2004, Voulgaris 2005], but the relationship is the same whether changes in CPP resulted from changes in ICP or ABP [Chan 1992]. The influence of systemic haemodynamics on PI, that is upstream forces, has also been demonstrated [Evans 1980, Rossitti 1995, Gooskens 2003]. At least, experimental data demonstrated that PI is in fact dependant on ICP, on ABP, consequently on CPP and on vascular tone (CO2) [Czosnyka 1996]. To summarize, changes in PI are correlated to both changes in ICP and ABP. Although few papers favour PI as a surrogate ICP, the sensitivity of PI to identify raised ICP is high, but its specificity is low. Diastolic flow velocity Pulsatility index SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

16 CD waveform analysis for the evaluation of intracranial pressure
PULSATILITY INDEX SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

17 T CD for ICP EVALUATION Σ
The pulsatility of blood flow through conductance vessels reflects distal vascular resistance. Gosling et al. 1969 PULSATILITY INDEX IS LESS SUSCEPTIBLE TO FACTORS THAT INFLUENCE FLOW VELOCITY MEASUREMENTS SUCH AS THE ANGLE OF INSONATION. PI is a dimensionless TCD variablederivedfrom the differencebetweensistolic and diastolic flow velocitiesdividedby the meanvelocity, and itis a reflexionof CVR. When CPP falls due toincreased ICP, diastolic flow velocitiesdropbefore the sistolicresulting in anincrease in PI from the normalvalueof<1 to>1. Under normalconditionsofbloodpressure and arterialcarbondioxidetension, the pulsatilityofblood flow through the conductancevesselsreflectsdistalcerebrovascularresistancetherefore a PI can becalculatedwhichreflectsthis. The mostcommonlyusedmeasureis the Gosling’s indexwhichiscalculatedasfollows: The earliestsignofincreased ICP is increased pulsatility, followed by progressive reduction in diastolic and mean flow velocities. Increased ICP and cerebral circulatory arrest. There is a qualitative relationship between progressive increases in ICP and the evolution of abnormal TCD waveforms, assuming a constant arterial CO2 content and a constant degree of distal vasoconstriction. Pulsatility changes occur when cerebral perfusion pressure is 70 mm Hg. The earliest sign of increased ICP is increased pulsatility, followed by progressive reduction in diastolic flow velocities and reduction in mean flow velocities. As regional or generalized ICP elevation becomes increasingly extreme, diastolic flow reaches zero, followed by an alternating flow pattern with retrograde diastolic flow, disappearance of diastolic flow, appearance of small systolic spikes, and eventually no flow. Once the reverberating flow pattern appears, cerebral blood flow disappears on angiography and brain death is likely. Evolutionary changes may occur over a period of minutes to hours.1, anarterialblood-flowvelocitywaveformindexdesignedtoquantify the pulsatility or oscillationsof the waveform. The indexisparticularlyvaluablewhenthereisdiastolic flow reversal, i.e. bidirectional flow. The originalpulsatilityindex (designedbyGosling, 1971) wasfairlycomplex, and a simplifiedversionisthereforeused in clinicalpractice. Differentdefinitionsofthissimplified PI maybefound in the literature, but the following formula iscommonlyused:PI = (Vmax - Vmin) / VmaxmeanwhereVmaxis the peaksystolicvelocity, Vminis the minimum forwarddiastolicvelocity in unidirectvanarterialblood-flowvelocitywaveformindexdesignedtoquantify the pulsatility or oscillationsof the waveform. The indexisparticularlyvaluablewhenthereisdiastolic flow reversal, i.e. bidirectional flow. The originalpulsatilityindex (designedbyGosling, 1971) wasfairlycomplex, and a simplifiedversionisthereforeused in clinicalpractice. Differentdefinitionsofthissimplified PI maybefound in the literature, but the following formula iscommonlyused:PI = (Vmax - Vmin) / VmaxmeanwhereVmaxis the peaksystolicvelocity, Vminis the minimum forwarddiastolicvelocity in unidirectional flow, or the maximum negative velocity in diastolic flow reversal, and Vmaxmeanis the maximumvelocityaveragedover (at least) onecardiac cycle (Fig.1). When PI is estimated from the time velocity spectral display of Doppler ultrasound, the time-averaged maximum velocity is usually calculated automatically after manual tracing of the maximum velocity envelope.The pulsatility index is commonly used in the evaluation of renal transplant rejection. An increase in PI suggests increased vascular resistance, a characteristic, but not pathognomonic, feature of acute rejection. PI is also much used in evaluation of peripheral vascular disease. A decrease in the waveform pulsatility may indicate upstream stenosis.HJSional flow, or the maximum negative velocity in diastolic flow reversal, and Vmaxmeanis the maximumvelocityaveragedover (at least) onecardiaccycle (Fig.1. When PI is estimated from the time velocity spectral display of Doppler ultrasound, the time-averaged maximum velocity is usually calculated automatically after manual tracing of the maximum velocity envelope.The pulsatility index is commonly used in the evaluation of renal transplant rejection. An increase in PI suggests increased vascular resistance, a characteristic, but not pathognomonic, feature of acute rejection. PI is also much used in evaluation of peripheral vascular disease. A decrease in the waveform pulsatility may upstrea stenosis.HJS Σ N A2n 1 A2 n=1 PI = SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

18 Peak to peak amplitude of the Doppler shift recording
INDICA L’ANDAMENTO DELLA CURVA DI VELOCITA’ DURANTE UN CICLO CARDIACO Gosling RG, King DH. Arterial assessment by Doppler Shift ultrasound. ProcRsoc Med 1974;67:447–9. Peak to peak amplitude of the Doppler shift recording Mean value PI = SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

19 CD for non invasive ICP EVALUATION
During elevated ICP the arterioles are easely compressed creating a high peripheral vascular resistance reducing the flow and thereby the denominator of PI. The numerator derives from the differance between systolic and diastolic FV. In a rigid tube the pressure is directly proportional to FV, as in Diabetic micrangiopathy where the vessel compliance is depressed (Lee et al. Arterial pulsatility as an index of cerebral microangiopathy in diabetes. Stroke 2000;31: An increased ICP always results in reduced compliance of the entire brain tissue including increased rigidity of the brain arteries augmenting the velocity variations, which in turn increases the denominator of PI. Consequently this index is sensitive ti ICP. Under normalconditionsofbloodpressure and arterialcarbondioxidetension, the pulsatilityofblood flow through the conductancevesselsreflectsdistalcerebrovascularresistancetherefore a PI can becalculatedwhichreflectsthis. The mostcommonlyusedmeasureis the Gosling’s indexwhichiscalculatedasfollows: The earliestsignofincreased ICP is increased pulsatility, followed by progressive reduction in diastolic and mean flow velocities. Increased ICP and cerebral circulatory arrest. There is a qualitative relationship between progressive increases in ICP and the evolution of abnormal TCD waveforms, assuming a constant arterial CO2 content and a constant degree of distal vasoconstriction. Pulsatility changes occur when cerebral perfusion pressure is 70 mm Hg. The earliest sign of increased ICP is increased pulsatility, followed by progressive reduction in diastolic flow velocities and reduction in mean flow velocities. As regional or generalized ICP elevation becomes increasingly extreme, diastolic flow reaches zero, followed by an alternating flow pattern with retrograde diastolic flow, disappearance of diastolic flow, appearance of small systolic spikes, and eventually no flow. Once the reverberating flow pattern appears, cerebral blood flow disappears on angiography and brain death is likely. Evolutionary changes may occur over a period of minutes to hours.1, anarterialblood-flowvelocitywaveformindexdesignedtoquantify the pulsatility or oscillationsof the waveform. The indexisparticularlyvaluablewhenthereisdiastolic flow reversal, i.e. bidirectional flow. The originalpulsatilityindex (designedbyGosling, 1971) wasfairlycomplex, and a simplifiedversionisthereforeused in clinicalpractice. Differentdefinitionsofthissimplified PI maybefound in the literature, but the following formula iscommonlyused:PI = (Vmax - Vmin) / VmaxmeanwhereVmaxis the peaksystolicvelocity, Vminis the minimum forwarddiastolicvelocity in unidirectvanarterialblood-flowvelocitywaveformindexdesignedtoquantify the pulsatility or oscillationsof the waveform. The indexisparticularlyvaluablewhenthereisdiastolic flow reversal, i.e. bidirectional flow. The originalpulsatilityindex (designedbyGosling, 1971) wasfairlycomplex, and a simplifiedversionisthereforeused in clinicalpractice. Differentdefinitionsofthissimplified PI maybefound in the literature, but the following formula iscommonlyused:PI = (Vmax - Vmin) / VmaxmeanwhereVmaxis the peaksystolicvelocity, Vminis the minimum forwarddiastolicvelocity in unidirectional flow, or the maximum negative velocity in diastolic flow reversal, and Vmaxmeanis the maximumvelocityaveragedover (at least) onecardiac cycle (Fig.1). When PI is estimated from the time velocity spectral display of Doppler ultrasound, the time-averaged maximum velocity is usually calculated automatically after manual tracing of the maximum velocity envelope.The pulsatility index is commonly used in the evaluation of renal transplant rejection. An increase in PI suggests increased vascular resistance, a characteristic, but not pathognomonic, feature of acute rejection. PI is also much used in evaluation of peripheral vascular disease. A decrease in the waveform pulsatility may indicate upstream stenosis.HJSional flow, or the maximum negative velocity in diastolic flow reversal, and Vmaxmeanis the maximumvelocityaveragedover (at least) onecardiaccycle (Fig.1. When PI is estimated from the time velocity spectral display of Doppler ultrasound, the time-averaged maximum velocity is usually calculated automatically after manual tracing of the maximum velocity envelope.The pulsatility index is commonly used in the evaluation of renal transplant rejection. An increase in PI suggests increased vascular resistance, a characteristic, but not pathognomonic, feature of acute rejection. PI is also much used in evaluation of peripheral vascular disease. A decrease in the waveform pulsatility may upstrea stenosis.HJS The earliest sign of increased ICP is increased pulsatility. PI Normal value < 1 SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

20 CD for non invasive ICP EVALUATION
PI Ratio – therefore not infuenced by the angle of insonation influenced by certain factors that influences flow velocity Upstream - Downstream Hemodynamic Respiratory Hematologic Tissue compliance Parameters Increased with the increase of downstream resistance (vasocostriction, ICP) Reduced with the reduction of upstream blood supply (stenosis, CO, hypotension) The arterioles are greater influenced than in the larger vessels SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

21 aveform analysis of high ICP
W Resistenze, buona sensibilità, non altrettanto specificità. ICP- 20 ICP- 60 SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

22 s a waveform enough? I Can we be satisfied with a qualitative
measurment ? SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

23 O rigins of non invasive assessment
Houmburg AM. et al. Transcranial Doppler recording in raised intracranial pressure Acta Neurol Scand 1993:87: Chan KM et all. Transcranial Doppler waveform differences in hyperemic and non hyperemics patients after severe injury- Sur Neurol 1992;87:488-93 Klingelhofer J. et all Evaluation of intracranial pressure from transcranial Doppler studies in cerebral desease. J Neurosonol 1988;235:159-62

24 slid and the Fourier analysis
PA1= ampiezza della prima armonica dell’onda che descrive la pressione arteriosa FV1 = ampiezza della prima armonica dell’onda che descrive la velocità di flusso 10 pazienti < 27 mmHg  95% delle stime < 10 mmHg  52% delle stime una stima basato sulla SPI che puo essere interpretato come la differenza tre la ABP e la CCP, hanno modificat la formula per ottenere dei risultati migliori rispetto ad altre techniche. Aaslid et al 52% of the aCPP < 10mm Hg range. Schmidt E et al 80 % of the eCPP < 10 mm Hg range. A1 = first harmonic component of ABP pulse wave F1 = first harmonic component of CBFV pulse wave The first estimate was based on the SPI (F1/FVm) which can also be interpreted as the difference between ABP and CCP (calculated as ABPm – A1/F1 x FVm). The second formula cannot be directly related to CCP. A potential disadvantage of both methods is that they are unable to compensate for changes in vascular resistance as long as they do not exert a secondary impact on ABP or ICP. For example during hyperventilation vascular resistance changes and therefor so does the pulsatility index. Aaslid R. et all Estimation of cerebral perfusion pressure from arterial blood pressure and transcranial Doppler recordings in Intracranial pressur IV Berlin Spnger-Verlag 1986 pp226-29

25 C ambridge proposal PAM = pressione arteriosa media
FVd = Velocità di flusso diastolica FVm = Velocità di flusso media SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

26 C ambridge proposal 25 pazienti ≤ 5 mmHg  49% ≤ 10 mmHg  81%
Czosnyka M, et al. Cerebral perfusion pressure in head injured patients: a non invasive assessment using transcranial doppler ultrasonography. J Neurosurg 1998; 88:802-8 Schmidt EA et all. Preliminary experience of the estimation of cerebral perfusion pressure using transcranial Doppler ultrasonography J Neurol Neurosurg and Psycjiatry 2001;170:198204 SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

27 T CD for CPP EVALUATION Aaslid et al Czosnykaet al. < 27 mmHg  95%
Whatweuseis the following…TCDhas been frequently employed for the clinical evaluation of cerebral vasospasmfollowingsubarachnoidhaemorrhage (SAH). To a lesser degree, TCD has also been used toevaluatecerebralautoregulatorycapacity, monitor cerebralcirculationduringcardiopulmonary bypass and carotidendarterectomies and to diagnose brain death. Technological advances such as M mode, colour Doppler and three-dimensional power Doppler ultrasonographyhave extended the scope of TCD to include other non-critical care applicationsincludingassessment of cerebral emboli, functional TCD and the management of sickle cell disease. Newerdevelopments in thistechnology include venous Doppler, functional Doppler and use of ultrasound contrast agents. Aaslid and colleagues (1982) introducedtranscranial Doppler (TCD) ultrasonographyinto clinical practice for the evaluation of cerebral haemodynamics, ushering in a new era of cerebral circulationmonitoring [2]. CPP is the difference between arterial pressure (AP) and the effective downstream pressure (EDP) of the cerebral circulation. Because of a Starling resistor phenomenon located at the level of cerebral veins ICP is thought to represent the EDP of the cerebral circulation [23]. Estimationofcerebralperfusionpressurefromarterialbloodpressure and transcranial Doppler recordings in Intracranialpressure. Aaslid R. et al. Heidelberg, New York, BerlinSpringer-Verlag 1986 pp226-29 Several methods of estimating CPP using measured TCD velocitieshavebeendescribed: Aaslidet al. [25] determined CPP using the following TCD parameters: where F1 and A1 represent amplitude of the fundamental frequency components of FV and arterial pressure, respectively. The fundamental frequency is determined by fast Fourier analysis of the waveform, and is equivalent to the heart rate. Czosnyka et al. [26] used measured and calculated TCD variables from 96 patients with head injury to derive a different formula to estimate CPP: using time averaged mean, systolic and diastolic values of FV from the MCA. A subsequent validation study of the above method reported the absolute difference between measured CPP and calculated CPP (daily averages) to be less than 10 mmHg in 89% of measurements and less than 13 mmHg in 92% of measurements [27]. Edouard et al. [28] investigated a simplified model of CPP originally described in pregnant patients. They compared conventional measurements of CPP (difference betweenMAP and ICP) with an estimated CPP (CPPe). CPPe was derived using a formula combining the phasic values of FV and arterial pressure: CPPe = vmeanvmean − vdiast × (APmean − APdiast) (6) where vmean and vdiast are the mean and diastolic MCA velocities, and APmean and APdiast are the mean and diastolic arterial pressures, respectively. Twenty adults with bilateral and diffuse brain injuries were included in the study. CPPe and CPP were correlated (slope intercept +10.9, 95% CI 3.5 to +25.4). The intercept of the regression line equaled the zero flow pressure (ZFP), in theMCA and represents the EDP of the cerebral circulation. Noninvasive measurement of CPP is a promising technique. Current evidence suggests that EDP as predicted by the critical closing pressure is as useful as ICP in describing cerebral haemodynamics, and in some instances better. Weyland et al. [29] observed that during hypocapniacerebrovascular tone rather than ICP determines the EDP and therefore CPP. Thus MAP EDP would give a better indication of CPP in this situation. More work is needed as none of the recently described methods has been fully validated; in particular, it is not clear from the existing literature which formula is most appropriate under given pathophysiologicalconditions. < 27 mmHg  95% < 10 mmHg  52% < 21 mmHg  95% dellestime < 10 mmHg  81% dellestime SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

28 OUR RESULTS 21 pazienti 530 stime
SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

29 CD for non invasive ICP EVALUATION
Head Trauma Brain Infarct Menengtis /Encephalytis Decompressive Craniectomy SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

30 CD for non invasive ICP EVALUATION
Literature suggests that the PI is useful as a non invasive estimate of ICP and CPP in adult TBI and SAH Bellner J et al. Transcranial Doppler sonography pulsatility index (PI) reflects intracranial pressure (ICP). Surg Neurol 2004;62:45,51. Splavski B et al. Transcranial Doppler ultrasonography as an early outcome forecaster following severe brain injury. Br J Neurosurg 2006; 20: Ract C et al. Transcranial Doppler ultrasound goal-directed therapy for the early management of severe traumatic brain injury. Inten Care Med 2007;33: SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

31 CD for non invasive ICP EVALUATION
et al. First prospective study to investigate the relationship between ICP and TCD derived PI. ICP higher than 20 mm Hg could be detected with a sensitivity of 0.89 and specificity of 0.92. SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

32 CD for non invasive ICP EVALUATION
There is a strong correlation between PI and ICP ( ICP values > 20 mmHg ), and between PI and CPP ( CPP values < 70 mmHg). Voulgaris et al. SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

33 CD for non invasive ICP EVALUATION
TALIP ASIL et al. - Increased PI correlated with midline shifts on CT scans. Now as I mentioned in the beginning, measuring ICP is not necessarely only useful in head trauma… TCD was reported useful for monitoring ICP in patientswithlargesupratentorialinfarctions Gerriets T. SupratentorialhemisphericinfarctionsMalignantcerebraledema = 10% Transtentorialherniationand brain death 3 and 5 days afterischemicstroke Early outcomes of pts who had increased PI were poorer. SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

34 T CD for non invasive ICP EVALUATION CBF CVR = FV + PI
Cerebral hemodynamic changes gauged by transcranial Doppler ultrasonography in patients with post-traumatic brain swelling treated by surgical decompression EdsonBor-Seng-Shuet al. J Neurosurg 104:93-100, 2006 CVR = FV PI CBF SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

35 CD for non invasive ICP EVALUATION
INTERHEMISPHERIC PRESSURE GRADIENTS TRANSMANTLE PRESSURE GRADIENTS PRESSURE GRADIENTS BETWEEN THE SUPRA AND INFRATENTORIAL SPACES PRESSURE GRADIENTS WITHIN THE CEREBROSPINAL AXIS SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

36 CD for non invasive ICP EVALUATION
Cardoso ER, Kupchak JA. Evaluation of intracranial pressure gradients by means of transcranial Doppler sonography. Acta Neurochir 1992; 55 (Suppl): 1-5. Intracranial pressure gradients generated by mass lesions are responsible for the asymmetry of TCD readings. Cardoso ER, Kupchak JA. Cerebral Hydrodynamics Research Laboratory, Health Sciences Centre, Winnipeg, Manitoba, Canada. The authors investigated the effects of intracranial pressure gradients generated by a unilateral intracranial mass on transcranial Doppler (TCD) readings. Eleven patients harbouring a symptomatic chronic or subacute subdural haematoma underwent pre- and post-operative TCD examinations of the intracranial internal carotid and middle cerebral arteries. Mean values of velocity and pulsatility index (PI) were compared to the contra-lateral counterpart. The haematomas were evacuated by means of burr hole drainage under local anaesthesia. Symptomatic subdural haematomas lowered the ipsilateral blood velocity in the internal carotid and middle cerebral arteries by a mean side-to-side difference of / m.sec-1. The ipsilateral PI was higher than the contralateral values by an average of / Low mean velocity and high PI values were associated with high subdural pressure. Abnormal pre-operative ipsilateral TCD readings returned to normal following haematoma drainage. We postulate that intracranial pressure gradients generated by the subdural mass lesion are responsible for the asymmetry of TCD readings. These differences should be considered in the interpretation of post-subarachnoid haemorrhage vasospasm, as it is frequently associated with lateral clots. Our findings also provide a useful method for non-invasive monitoring of intracranial pressure gradients. PMID: [PubMed - indexed for MEDLINE] SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

37 CD for non invasive ICP EVALUATION
SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

38 CD for non invasive ICP EVALUATION
SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

39 PI CBF ABP Critical Closing Pressure 5 50 160 CBF = CPP/R
TCD identification of changing autoregulatory thresholds after autoregulatory impairment. Lewis SB et al. Neurosurgery 2001:49(6); CBF Maximum Vasoconstriction R = Rmax Maximum Vasodilation R = Rmin PI Several studies suggest, that the pulsatility index of the transcranial Doppler may be useful in determining the lower autoregulatory threshold [17,20,24]. When CPP approaches the lower autoregulatory limit, the PI starts to increase rapidly because of the increase in the numerator and a decrease in the denominator, whereas vascular resistance reaches its minimum level. Chan et al. [12,17] observed from measurements in patients with severe TBI that the Gosling PI increased slightly when they reduced CPP within the autoregulation range (CPP >50 mmHg), but it exhibits a disproportionate increase at low CPP levels. Treatment to increase the CPP caused the PI to fall with normal range [24]. In our study, as CPP decreased from 70 mmHg, the strongest inverse correlation between CPP and PI was obtained. At CPP values above 70 mmHg a very weak correlation between CPP and PI was observed. This fact indicates that the pulsatility index had a high predictive value for detecting low CPP (<70 mmHg). Critical Closing Pressure 5 50 mmHg 160 mmHg ABP CBF = CPP/R SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

40 CD for Emergency ICP EVALUATION
SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

41 CD for Emergency ICP EVALUATION
Admission FVd< 25 cm/s and PI > 1.3 is associated with a poor outcome Trabold et al. Admission velocities, FVm< 30 cm/s, were related to GCS, and correctly predicted early outcome. Chan KH et al. SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

42 CD for Emergency ICP EVALUATION
We investigated 37 patients with severe TBI (GCS <8 on admission). The TCD parameters included the systolic, diastolic, and mean velocities of the middle cerebral artery (MCV) and the pulsatility index (PI). Mean arterial pressure (MAP), ICP, CPP, and simultaneous arterial and venous blood gases were also measured. Results: We observed a strong correlation between ICP and PI (r=0.82, p<0.0001) for ICP values >20 mmHG. The correlation of CPP to PI were also statistically signifi cant (P<0.0001).The strongest inverse correlation between CPP and PI was obtained (r=0.86, p<0.0001) for CPP values below 70 mmHg. Conclusions: Pulsatility index measurements permit the early identification of patients with low CPP and high risk of cerebral ischemia. In emergency situations it can be used alone when ICP monitoring is contraindicated or not readily available. SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

43 CD for Emergency ICP EVALUATION
24 TBI pts. Anormal TCD values (group 1) Normal TCD values (group 2) 3-month GOS was significantly poorer in group 1 than in group 2. TCD wasconsideredabnormal when two out of three measured values were outside the following limits: Vm< 30 cm/s, Vd< 20 cm/s, PI > 1.4. SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

44 Comparison of TCD and Ultrasound for non-invasive estimation of intracranial hypertension and its prediction during the early phase following severe head trauma. TCD ECO ? ICP SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

45 Arteriolar resistance vessels
TCD & Critical Closing Pressure MABP CVP P = T/r P = pressione transmurale T = tensione di parete r = raggio del vaso P < T/r  MAP  ICP  Tono vasomostore 2° STARLING RESISTOR bridging Veins = MAP - ICP CPP = MAP - CCP CPP 1° STARLING RESISTOR Arteriolar resistance vessels SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

46 TCD and CCP TCD can be used to derive CCP Although not yet confirmed as a clinically useful parameter, it does have much potential for the future Zero flow was derived from the beat to beat analysis of instantaneous pressure/flow velocity (AP/Vmca) plots. Pressure and flow velocity of single heart beats were plotted against each other and extrapolated to zero flow velocity using linear reggression analysis. Weyland A. et all Cerebrovascular tone rather than intracranialpressure determinesthe effective downstreampressure of the cerebralcirculation in the absence of intracranial hypertension J Neurosurg Anesth 2000;12:210-16 SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

47 flusso TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA
SSVD Neurorianimazione ,Spedali Civili, Brescia, Dr. FRANK RASULO TCD PER LA DIAGNOSI DI IPERTENSIONE INTRACRANICA

48 T C D

49


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