**7. Transcranial Doppler - TCD**

Transcranial Doppler (TCD) was developed in Switzerland in 1982 by Aaslid et al. [28]. A low frequency transducer (≤2 MHz) emits and receives ultrasound waves able to pass through skull bone and allow hemodynamic brain evaluation noninvasively2, through the observation of arterial blood flow systolic and diastolic velocities (**Figure 4**). With the introduction of TCD in Neurology, Neurosurgery and Intensive Care, new frontiers were opened to the understanding of the physiopathology of the various diseases associated with the dynamics of brain blood flow. TCD is performed at the bedside, has low cost and can be repeated whenever necessary without the need for patient transport, allowing the diagnosis and evolutionary follow-up of cerebrovascular diseases.

The main applications of TCD for brain hemodynamic monitoring in adults and children are:


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*Management of Patients with Brain Injury Using Noninvasive Methods*

• evaluation in ischemic cerebrovascular disease with and without arterial

• ischemia mechanisms determination, whether arterial–arterial embolism, cardioembolic, arterial–venous shunting or hemodynamic [45, 46]

• measurement of hemodynamic repercussion in systemic diseases (sepsis and

**7.1 Hemodynamic indices of transcranial Doppler and functional evaluation**

Lindegaard Index (LI), Soustiel Index (SI) and breath-holding index (BHI). Mv is the central parameter of brain blood flow velocity spectrum analysis and is defined by the following formula: Mv = Sv + (Dv × 2)/3 [51] .Mv is a variable influenced by different physiological factors and its interpretation cannot be performed in isolation. Changes in Mv are due to age, sex, temperature, partial CO2 pressure (PaCO2), mean arterial pressure (MAP), hematocrit, pregnancy, presence of hypermetabolic states, and administration of anesthetic/sedative drugs. In general, there is an increase of the Mv from 6 to 10 years of age, then, there is a

The indexes calculated from the spectra of blood flow velocities obtained by TCD allow the characterization of brain circulatory patterns (**Table 1**). Thus, the following variables are analyzed: mean velocity (Mv), systolic velocity (Sv), diastolic velocity (Dv), Gosling Pulsatility Index (PI), Pourcelot Resistance Index (RI),

PI is the relationship between systole and diastole of the cerebral blood flow velocity spectrum. In situations where there are no cardiovascular pathologies and where there is no change in the diameter of the studied vessel, this index can be used to indirectly assess the integrity of the distal vascular bed and provide information on the microvascular brain resistance. It is calculated by the formula: Sv-Dv/Mv; its acceptable value ranges from 0.6 to 1.19 [53]. In stenosis or proximal occlusions, there may be a reduction in PI due to downstream arteriolar vasodilation. On the other hand, critical stenosis or distal occlusions, as well as microvascular vasoconstriction may be associated with PI elevation in proximal arterial segments. The PI below 0.5 may indicate the presence of intracranial arteriovenous malformation,

diseases, of intra- and extracranial arteries [43, 44],

*Spectral wave graph that has a peak systolic velocity (A) and final diastolic velocity (B).*

• risk of stroke evaluation and follow-up in sickle cell anemia16,

• complementary diagnosis of brain death [49, 50]

*DOI: http://dx.doi.org/10.5772/intechopen.94143*

liver failure) [47, 48]

**Figure 4.**

lifetime reduction [52].

*Management of Patients with Brain Injury Using Noninvasive Methods DOI: http://dx.doi.org/10.5772/intechopen.94143*

#### **Figure 4.**

*Advancement and New Understanding in Brain Injury*

the oxygenation status of the tissue.

cated signal interpretation.

**7. Transcranial Doppler - TCD**

pressure, etc.) [40, 41].

evolutionary follow-up of cerebrovascular diseases.

The basis of NIRS relies upon two principles:

1.that tissue is relatively transparent to near-infrared light and

2.that there are compounds in tissue in which absorption of light is dependent on

The propagation of light in tissue depends on the combination of absorption, scattering, and reflection properties of photons. Absorption and scatter in tissue is dependent on the wavelength. Scatter decreases with increasing wavelengths; thereby favoring the transmission of near-infrared light compared to visible light. NIRS, like most technology, has various limitations. The most important of those limitations are as follows: interference from non-targeted chromophores; indefinite differential path-length; unknown scattering loss factor; and compli-

Considering the pending technical challenges, the limited number of patients studied, and the conflicting results and opinions on this subject, we believe that this non-invasive method of predicting ICP should be restricted to research centers. Cerebral injury due to hypoxic/ischemic and hyperperfusion are common issues associated with clinical and surgical practice. Monitoring of cerebral oxygenation during surgery, e.g.; cardiac and cerebral endarterectomy, has been shown to

improve patient outcomes and reduce the risk of negative surgical outcomes. In addition to surgical monitoring, NIRS technology provides useful insight into cerebral hemodynamics when used in combination with other cerebral monitoring systems. NIRS monitoring and comparisons have been made with transcranial Doppler (TCD) and electroencephalography (EEG) in its ability to accurately predict cerebral ischemia and hyperperfusion. In addition to perioperative monitoring in clinical settings, many researchers utilize the various NIRS systems to reflect on the cerebral tissue oxygenation status during environmental and exercise interventions

Transcranial Doppler (TCD) was developed in Switzerland in 1982 by Aaslid et al. [28]. A low frequency transducer (≤2 MHz) emits and receives ultrasound waves able to pass through skull bone and allow hemodynamic brain evaluation noninvasively2, through the observation of arterial blood flow systolic and diastolic velocities (**Figure 4**). With the introduction of TCD in Neurology, Neurosurgery and Intensive Care, new frontiers were opened to the understanding of the physiopathology of the various diseases associated with the dynamics of brain blood flow. TCD is performed at the bedside, has low cost and can be repeated whenever necessary without the need for patient transport, allowing the diagnosis and

The main applications of TCD for brain hemodynamic monitoring in adults and

• functional evaluation of intracranial circulation by estimating cerebral perfusion pressure and reactivity tests at different stimuli (CO2, arterial

• subarachnoid hemorrhage (HSA)6, head trauma and other diseases that may occur with intracranial hypertension and segmental vessel stenosis [42]

despite strong evidence and proper analytical techniques [36, 39].

**104**

children are:

*Spectral wave graph that has a peak systolic velocity (A) and final diastolic velocity (B).*


#### **7.1 Hemodynamic indices of transcranial Doppler and functional evaluation**

The indexes calculated from the spectra of blood flow velocities obtained by TCD allow the characterization of brain circulatory patterns (**Table 1**). Thus, the following variables are analyzed: mean velocity (Mv), systolic velocity (Sv), diastolic velocity (Dv), Gosling Pulsatility Index (PI), Pourcelot Resistance Index (RI), Lindegaard Index (LI), Soustiel Index (SI) and breath-holding index (BHI).

Mv is the central parameter of brain blood flow velocity spectrum analysis and is defined by the following formula: Mv = Sv + (Dv × 2)/3 [51] .Mv is a variable influenced by different physiological factors and its interpretation cannot be performed in isolation. Changes in Mv are due to age, sex, temperature, partial CO2 pressure (PaCO2), mean arterial pressure (MAP), hematocrit, pregnancy, presence of hypermetabolic states, and administration of anesthetic/sedative drugs. In general, there is an increase of the Mv from 6 to 10 years of age, then, there is a lifetime reduction [52].

PI is the relationship between systole and diastole of the cerebral blood flow velocity spectrum. In situations where there are no cardiovascular pathologies and where there is no change in the diameter of the studied vessel, this index can be used to indirectly assess the integrity of the distal vascular bed and provide information on the microvascular brain resistance. It is calculated by the formula: Sv-Dv/Mv; its acceptable value ranges from 0.6 to 1.19 [53]. In stenosis or proximal occlusions, there may be a reduction in PI due to downstream arteriolar vasodilation. On the other hand, critical stenosis or distal occlusions, as well as microvascular vasoconstriction may be associated with PI elevation in proximal arterial segments. The PI below 0.5 may indicate the presence of intracranial arteriovenous malformation,


**Table 1.** *Brain hemodynamic indexes.*

since the resistance in the proximal vessels is reduced due to the absence of brain tissue between arterioles and venules. PI can correlate positively with intracranial pressure (ICP); changes of 2.4% in PI may reflect a variation of 1 mmHg in PIC. The RI is calculated by the following formula: Sv-Dv/Sv. In practice, it has the same function of PI and values greater than 0.8 indicate an increase downstream of resistance to blood flow [54].

LI is defined as the relationship between the Mv of the middle cerebral artery and the Vm of the ipsilateral extracranial internal carotid artery. In the condition of significant increase of Mv in the middle cerebral arteries, this index allows the differentiation between hyperdynamic blood flow and vasospasm [55]. A LI lower than 3 may suggest hyperdynamic blood flow and an LI greater than 3 may suggest narrowing of an artery segment as occurs in vasospasm. SI consists of the relationship between the Mv of the basilar artery and the extracranial vertebral artery. This index is used for the diagnosis of vasospasm in the posterior brain circulation. These indices together with Mv in the studied arteries are also used to classify the degree/severity of vasospasm, as shown in **Table 2**.

#### *7.1.1 Reactivity test*

BHI or voluntary apnea Index evaluates CO2 reactivity and is given by the following formula: (Mv after apnea - baseline Mv) /baseline Mv) × 100/30, in which 30 represents time in seconds of voluntary apnea performed by the patient. This index evaluates brain circulatory reactivity to hypercapnia (CVR), that is, the vasodilator capacity of brain circulation during elevation of carbon dioxide induced by apnea. BHI > 0.6 indicates preserved CVR, between 0.21 and 0.60 indicates compromised reactivity, and ≤ 0.20 reserves significantly compromised. Impairment of CVR may be related to a higher risk of cerebral ischemia caused by hemodynamic mechanism [56].

#### *7.1.2 Noninvasive estimation of cerebral perfusion pressure*

Several studies have shown that the measurement of blood flow velocities in the middle cerebral arteries by TCD allows an alternative noninvasive method of estimating cerebral perfusion pressure (eCPP) with high positive predictive value and low negative predictive value. The estimation of eCPP by TCD uses a method that involves Fourier's analysis of the first harmonic of the waveforms of both systemic blood pressure and the velocity of blood flow in the middle cerebral artery [57].

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*Management of Patients with Brain Injury Using Noninvasive Methods*

Several studies have demonstrated an adequate correlation between TCD to estimate eCPP and invasive measurement through the ICP catheter. Therefore, it has been proposed as a safe technique with the potential benefit of allowing intermittent or continuous analysis through monitoring. It can be used in situations where invasive measurement cannot be performed or when eCPP does not appear to be real or questionable. It is a robust, noninvasive method and allows qualitative analysis of CBF and tissue perfusion. Therefore, it can be used as an important guide for clinical

**Vasospasm severity (MCA) Mv (cm/s) LI** Take 120–130 3rd-3.9th Moderate 131–180 4–6 Serious >180 >6 **Vasospasm Severity (AB) Mv (cm/s) SI** Take 70–85 2–2.49 Moderate >85 2.5–2.99 Serious >85 >3 *MCA - middle cerebral artery; BA - basilar artery; Mv - mean velocity; LI - Lindegaard Index; SI - Soustiel Index.*

Patients with SAH may experience cerebral blood flow and metabolic changes that may culminate in increased intracranial pressure and ischemia. Three hemodynamic stages can be identified in this context: hyperemia, oliguemia and vasospasm. With TCD recognition of hemodynamic stages, physicians can be guided for

In general, in the first 24 hours, there is an overall decrease in cerebral blood flow (CBF) which may be due to two mechanisms: increased intracranial pressure associated with reduced cerebral perfusion pressure and intense microvascular constriction associated with low concentrations of nitric oxide (NO). These phenomena can trigger tissue hypoperfusion, decreased supply of tissue O2 with

TCD in the hyper-acute phase of SAH may demonstrate cerebral oliguemia status. Thus, it helps decision-making in clinical conduct to be adopted, such as: 1) management of mean arterial pressure (MAP) more appropriate; 2) avoid hyperventilation, which in turn will cause hypocapnia and further reduction of CBF; and 3) avoid states that increase brain tissue metabolic demand (e.g. fever, seizure, etc.).

Brain microcirculatory vasodilation causes overall elevation of CBF. States of brain hyperemia may signal neurovascular decoupling and autoregulation impairment due to brain or systemic tissue acidosis and, in general, occurs 24 hours after

management of patients who are victims of acute brain injury [58].

**7.2 Subarachnoid hemorrhage (SAH)**

*Diagnostic criteria for vasospasm by CTD.*

optimal patient treatment [59].

*7.2.1 Oliguemia stage*

**Table 2.**

consequent ischemia.

*7.2.2 Hyperemia stage*

the state of oliguemia.

*DOI: http://dx.doi.org/10.5772/intechopen.94143*

*Management of Patients with Brain Injury Using Noninvasive Methods DOI: http://dx.doi.org/10.5772/intechopen.94143*


#### **Table 2.**

*Advancement and New Understanding in Brain Injury*

**Index Formula**

Average speed (Mv) Mv = Sv + (Dv × 2)/3 Pulsatility Index (PI) IP = Sv - Dv / Mv Resistance Index (RI) IR = Sv – Dv / Sv

Soustiel Index (SI) IS = BA Mv / VA Mv

resistance to blood flow [54].

*Dv - diastolic velocity.*

*Brain hemodynamic indexes.*

**Table 1.**

*7.1.1 Reactivity test*

hemodynamic mechanism [56].

degree/severity of vasospasm, as shown in **Table 2**.

*7.1.2 Noninvasive estimation of cerebral perfusion pressure*

since the resistance in the proximal vessels is reduced due to the absence of brain tissue between arterioles and venules. PI can correlate positively with intracranial pressure (ICP); changes of 2.4% in PI may reflect a variation of 1 mmHg in PIC. The RI is calculated by the following formula: Sv-Dv/Sv. In practice, it has the same function of PI and values greater than 0.8 indicate an increase downstream of

Breath-holding index (BHI) BHI = (Mv after apnea - Baseline Mv) / Baseline Mv) × 100/30 *MCA - middle cerebral artery; BA - basilar artery; VA - vertebral artery; Mv – mean velocity; Sv - systolic velocity;* 

Lindegaard Index (LI) IL = MCA Mv / extracranial ipsilateral ICA Mv

LI is defined as the relationship between the Mv of the middle cerebral artery and the Vm of the ipsilateral extracranial internal carotid artery. In the condition of significant increase of Mv in the middle cerebral arteries, this index allows the differentiation between hyperdynamic blood flow and vasospasm [55]. A LI lower than 3 may suggest hyperdynamic blood flow and an LI greater than 3 may suggest narrowing of an artery segment as occurs in vasospasm. SI consists of the relationship between the Mv of the basilar artery and the extracranial vertebral artery. This index is used for the diagnosis of vasospasm in the posterior brain circulation. These indices together with Mv in the studied arteries are also used to classify the

BHI or voluntary apnea Index evaluates CO2 reactivity and is given by the following formula: (Mv after apnea - baseline Mv) /baseline Mv) × 100/30, in which 30 represents time in seconds of voluntary apnea performed by the patient. This index evaluates brain circulatory reactivity to hypercapnia (CVR), that is, the vasodilator capacity of brain circulation during elevation of carbon dioxide induced by apnea. BHI > 0.6 indicates preserved CVR, between 0.21 and 0.60 indicates compromised reactivity, and ≤ 0.20 reserves significantly compromised. Impairment of CVR may be related to a higher risk of cerebral ischemia caused by

Several studies have shown that the measurement of blood flow velocities in the middle cerebral arteries by TCD allows an alternative noninvasive method of estimating cerebral perfusion pressure (eCPP) with high positive predictive value and low negative predictive value. The estimation of eCPP by TCD uses a method that involves Fourier's analysis of the first harmonic of the waveforms of both systemic blood pressure and the velocity of blood flow in the middle cerebral artery [57].

**106**

*Diagnostic criteria for vasospasm by CTD.*

Several studies have demonstrated an adequate correlation between TCD to estimate eCPP and invasive measurement through the ICP catheter. Therefore, it has been proposed as a safe technique with the potential benefit of allowing intermittent or continuous analysis through monitoring. It can be used in situations where invasive measurement cannot be performed or when eCPP does not appear to be real or questionable. It is a robust, noninvasive method and allows qualitative analysis of CBF and tissue perfusion. Therefore, it can be used as an important guide for clinical management of patients who are victims of acute brain injury [58].

### **7.2 Subarachnoid hemorrhage (SAH)**

Patients with SAH may experience cerebral blood flow and metabolic changes that may culminate in increased intracranial pressure and ischemia. Three hemodynamic stages can be identified in this context: hyperemia, oliguemia and vasospasm. With TCD recognition of hemodynamic stages, physicians can be guided for optimal patient treatment [59].

#### *7.2.1 Oliguemia stage*

In general, in the first 24 hours, there is an overall decrease in cerebral blood flow (CBF) which may be due to two mechanisms: increased intracranial pressure associated with reduced cerebral perfusion pressure and intense microvascular constriction associated with low concentrations of nitric oxide (NO). These phenomena can trigger tissue hypoperfusion, decreased supply of tissue O2 with consequent ischemia.

TCD in the hyper-acute phase of SAH may demonstrate cerebral oliguemia status. Thus, it helps decision-making in clinical conduct to be adopted, such as: 1) management of mean arterial pressure (MAP) more appropriate; 2) avoid hyperventilation, which in turn will cause hypocapnia and further reduction of CBF; and 3) avoid states that increase brain tissue metabolic demand (e.g. fever, seizure, etc.).

#### *7.2.2 Hyperemia stage*

Brain microcirculatory vasodilation causes overall elevation of CBF. States of brain hyperemia may signal neurovascular decoupling and autoregulation impairment due to brain or systemic tissue acidosis and, in general, occurs 24 hours after the state of oliguemia.

TCD is able to identify the state of cerebral circulatory hyperdynamia and, consequently, guide the management of the hemodynamic condition of patients in order to avoid brain swelling associated with this condition. At this stage, situations that worsen the condition of brain hyperemia, such as hypercapnia, systemic arterial hypertension, anemia, and hypermetabolic brain conditions (e.g., seizure) should be avoided. In the study of cerebral autoregulation (CAR) the ability of the brain to maintain constant blood flow dynamics regardless of variations in systemic blood pressure is evaluated. SAH is one of the pathologies in which ra is impaired, which requires adequate systemic blood pressure levels to prevent hyperemia or oliguemia. TCD can identify CAR impairment through the relationship between flow velocity oscillations in the face of MAP changes (spontaneous or provoked); and this analysis is performed through modeling used in signals analysis, requiring the use of specific software for this purpose. Thus, TCD can help identify the most appropriate blood pressure range in impaired states.

#### *7.2.3 Vasospasm stage*

Vasospasm in SAH is one of the main causes of late cerebral ischemia. Therefore, its early recognition is mandatory in the clinical management of neurocritical patients. Before symptoms arise, vasospasm can be detected by TCD. Thus, clinical treatment of vasospasm can be instituted early, before the installation of neurological deficits.

There are several reasons that determine late cerebral ischemia in SAH-related vasospasm: 1) vasospasm intensity; 2) occurrence in multiple arteries or sequential vasospasm in "Tanden"; 3) presence or absence of activated collateral circulation; 4) early onset of vasospasm; 5) fast vasospasm progress (elevation of >25 cm/s/day); 6) associated tissue hypermetabolism; 7) mitochondrial tissue dysfunction; 8) presence of intracranial hypertension; 9) associated circulatory oliguemia; 10) impaired brain microcirculatory reserve; 11) preexistence of intracranial stenosis [60].

TCD is capable of detecting vasospasm in the middle and basilar cerebral arteries with high sensitivity and specificity [60]. Classically, vasospasm can occur between 4 and 14 days after the day of bleeding, and in some cases (13% of patients) can be detected early in the first 48 hours or late after 17 days. The possibility of monitoring vasospasm intensity may allow the optimization of clinical management. In severe vasospasm, the conjunction of other hemodynamic factors also observed by TCD determines the indication of, in addition to clinical measures, such as the use of vasoactive drugs and/or endovascular interventional treatment. The opportunity for the evolutionary follow-up of the response obtained to the treatment adopted is also an important benefit of TCD at this stage. **Table 2** shows the diagnostic and classification criteria of vasospasm severity by TCD using Mv and LI.

#### **7.3 Traumatic brain injury**

Intracranial circulatory abnormalities occur frequently in patients with TBI. Ischemic brain lesions can be identified in about 90% of patients who die after severe TBI [61], suggesting that changes in systemic and/or brain blood flow dynamics are frequent causes of ischemia and unfavorable outcomes. Studies of blood flow and brain metabolism suggest that hyperemic brain phenomena are the most frequently found in comatose patients after severe TBI [62].

#### *7.3.1 Brain hemodynamic phases after severe TBI*

As in SAH, there is a definition of 3 hemodynamic stages after severe TBI. The oliguemia stage occurs on the day of TBI (day 0) and is characterized by a reduction

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*Management of Patients with Brain Injury Using Noninvasive Methods*

in CBF. The hyperemia stage usually occurs on days one through three and is characterized by increased CBF. The vasospasm stage usually occurs from days 2 to 6 after

Cerebral changes in the acute stage of moderate or severe TBI, characterized by reduced blood flow velocity and increased PI in intracranial arteries, can be revealed by TCD, including during the first three hours after TBI occurrence. At this stage, TCD should be used early in order to guide therapeutic approaches. When oliguemia has been demonstrated, the possibilities of systemic blood pressure insufficiency of maintaining CBF dynamics (MAP below the autoregulation range), hyperventilation with reduction of partial arterial CO2 pressure, resulting in cerebral microvasculature vasoconstriction, posttraumatic thrombosis of the carotid arteries, and intracranial hypertension (especially if associated with increased PI) should be considered. The reduction in blood flow velocity in cerebral arteries may also be due to brain hypometabolism that may be associated with severe brain lesions. Presence of oliguemia may be associated with a higher risk of brain ischemia and an unfavor-

Cerebral hemodynamic patterns indicative of hyperemia can be detected by TCD in about 30% of patients during the first two weeks after severe TBI. The occurrence of this pattern is associated with worsening brain swelling and increased intracranial pressure. TCD can identify patients with posttraumatic brain hyperemia prior to the development of brain swelling, which allows the establishment of therapies aimed at minimizing neural tissue lesions secondary to ICH, such as the determination of the best mean arterial blood pressure range or the determination of the best PCO2 for a patient on mechanical ventilation. Persistence of hyperemia status may be associated with poor neurological

Studies with TCD in TBI estimate the occurrence of vasospasm in 50% of patients. There is an important association between vasospasm with severe hemodynamic repercussion and unfavorable neurological prognosis, although this repercussion is lower than in cases of spontaneous SAH. It is important to highlight that posttraumatic vasospasm of the basilar artery doubles the possibility of unfavorable prognosis, compared to patients without spasm of this artery. The duration of vasospasm in patients with TBI tends to be shorter due to the non-inflammatory nature as a cause, unlike subarachnoid hemorrhage. Possibly the origin of traumatic vasospasm is associated with stretching of the arteries during trauma and peak intensity, in many cases, occurs between the fifth and seventh day after trauma, although a duration similar to SAH is

Among other applications of TCD in severe TBI, it is worth mentioning: 1) to detect brain circulatory changes resulting from ICH; 2) to evaluate the degree of autoregulation and cerebrovascular reactivity impairment, enabling the prediction of prognosis; 3) to provide evidence of posttraumatic dissection or thrombosis of the arteries that irrigate the brain, allowing early investigation and adoption of

*DOI: http://dx.doi.org/10.5772/intechopen.94143*

TBI and there may be a reduction in CBF.

*7.3.1.1 Oliguemia stage*

able prognosis [63].

prognosis [64].

*7.3.1.3 Vasospasm phase*

observed in some cases [65].

*7.3.1.2 Hyperemia phase*

in CBF. The hyperemia stage usually occurs on days one through three and is characterized by increased CBF. The vasospasm stage usually occurs from days 2 to 6 after TBI and there may be a reduction in CBF.
