**3. TCD in aneurysmal subarachnoid hemorrhage**

Aneurysmal subarachnoid hemorrhage is a life-threatening condition that can result in significant morbidity and mortality. Vasospasm and delayed cerebral ischemia (DCI) are common complication of aSAH; they contribute to substantial morbidity and mortality after aSAH [1]. TCD can detect vasospasm by measuring changes in cerebral blood flow velocity with daily monitoring. A study found that TCD had high sensitivity and specificity in detecting vasospasm in aSAH patients [2]. DCI is another common complication of aSAH that can lead to poor outcomes. DCI is thought to be caused by vasospasm from endothelial dysfunction and microthrombosis [3, 4]. TCD can detect changes in cerebral blood flow velocity and microemboli associated with DCI to determine the appropriate timing of intervention such as intraarterial or oral calcium channel blockers to treat vasospasm in aSAH [5].

TCD measures blood flow velocity in all vessels in the circle-of-Willis, but especially for the MCA. Trends in the baseline TCD mean flow velocity (MFV) over time in patients with SAH are recommended for screening for vasospasm. MFV is most sensitive and specific for angiographic vasospasm in the MCA, whereas it is less sensitive and specific for the first segments of the ACA and PCA.

The Lindegaard ratio (or the hemispheric ratio) is the ratio of the MCA flow velocity to the ipsilateral ICA flow velocity. The ratio is often used in conjunction with MCA MFV and accounts for hemodynamic augmentation from a hyperdynamic state (e.g., from pressors or an endogenous hypersympathetic state). A Lindegaard ratio less than 3 suggests a hyperdynamic state with potential relative vasospasm as defined according to the MCA MFV (MCA MFV >120 cm/s indicates mild vasospasm; >150 cm/s, moderate; and >200 cm/s, severe). A Lindegaard ratio greater than 3 typically correlates with angiographic vasospasm seen on computed tomographic angiography (CTA) (>180 cm/s with perfusion impairment); a ratio greater than 6 indicates a high-grade angiographic spasm that may warrant an endovascular neurosurgery consultation.

With established normative data, TCD can be used to compare extracranial and intracranial flow velocities to help localize an intracranial stenosis as distinguished from a hyperdynamic state that is increasing the blood flow velocity (Lindegaard ratio = MCA flow velocity/distal extracranial ICA flow velocity; Soustiel ratio = BA flow velocity/distal extracranial VA flow velocity). Velocity trends are checked in each vessel daily and correlated with symptoms or radiographic spasm as a noninvasive means of investigating the "spasm window." Velocities usually increase in the first 3 days after bleeding and decrease at 9–14 days. All these provide daily monitoring of cerebral and systemic hemodynamics to guide optimal aSAH treatments.

While TCD is non-invasive, bedside procedure without need for contrast or radiation, it has several limitations. First, it is operator-dependent and often limited from craniotomy wound. Second, TCD correlates well with angiographic vasospasm but not necessarily with symptomatic vasospasm (i.e., clinical deficits). Many confounders are related to the systemic illness associated with aneurysmal SAH: increased ICP, hemodynamic instability, changes in PaCO2 or hematocrit, and collateralization. Despite these limitations, combining with other multimodal neuromonitoring for vasospasm and DCI, TCD adds tremendous value to the management of aneurysmal subarachnoid hemorrhage.

### **4. TCD in stroke for emboli detection**

Stroke is a major cause of morbidity and mortality worldwide. Early detection and treatment are crucial for improving outcomes in stroke patients. TCD has been used as a diagnostic tool to evaluate cerebral blood flow changes or microembolic in stroke patients to guide treatments. TCD can detect the presence of distal emboli from proximal intracranial or extracranial arterial stenosis or occlusions, and it can also monitor changes in cerebral blood flow velocity and wave form patterns during and after thrombolytic therapy for response and prognosticate outcomes.

In cervical carotid stenosis, several studies have shown that TCD can detect embolic signals in the middle cerebral artery, which is the most commonly affected site in carotid artery disease [6, 7]. Markus et al. found that asymptomatic cerebral emboli signals, high-intensity transient signals (HITS), were present in 58% of patients with symptomatic carotid artery disease and in 37% of patients with asymptomatic disease [6]. Same group also demonstrated asymptomatic cerebral emboli detection over 1 h in 200 patients with >50% symptomatic carotid stenosis was associated with 4.67-fold increased risk of recurrent ipsilateral ischemic events in adjusted cox regression model [7]. TCD is also utilized in predicting risk of stroke in patients with high-risk plaque features such as intraplaque hemorrhage. Sitzer et al. reported that plaque ulceration and lumen thrombus are the main sources of cerebral microemboli in high-grade internal carotid artery stenosis [8]. TCD can be used during carotid endarterectomy to detect emboli in real-time and guide the surgeon to take appropriate measures to prevent embolic events. Spencer et al. demonstrated that TCD could detect middle cerebral artery emboli during carotid endarterectomy, with a sensitivity of 92% and a specificity of 100% [9]. Therefore, TCD is a useful tool in the detection of cerebral emboli in carotid stenosis, which can help guide decision for intervention and surgical approach to minimize risk of stroke.

### **5. TCD for cerebrovascular reactivity**

Cerebrovascular reserve (CVR) is the ability of brain to autoregulate cerebral blood flow in response to physiologic changes such as arterial occlusion as in stroke. Impaired CV in patients with steno-occlusive disease is associated with increased

#### *Clinical Application of Transcranial Doppler in Cerebrovascular Diseases DOI: http://dx.doi.org/10.5772/intechopen.111665*

risk of stroke [10–12]. CVR quantified change in cerebral blood flow in response to vasodilatory stimuli such as carbon dioxide (CO2). Several multiple modalities for measuring CVR, including Blood Oxygen Level Dependent (BOLD) or arterial spin labeling (ASL) MR imaging with CO2 challenge, CT perfusion with acetazolamide. Among these noninvasive modalities, TCD is the most commonly used modality for assessing CVR and guiding decisions for revascularization. A systematic review involving 754 patients with asympatomic severe carotid stenosis and impaired CVR on TCD had 3.69 fold increased risk of ipsilateral ischemic stroke (HR 3.69, 95% CI 2.01–6.77, P < 0.001) [11].

CVR measured by TCD appears to be a useful tool for predicting outcomes after revascularization in patients with carotid stenosis or ICAD. However, due to the dynamic and time-variant nature of CVR, the influence of aging (normal or pathologic aging), exposure to common vasoactive agents such as caffefine or medications, and diurnal variation on CVR in relationship to cerebrovascular diseases is not yet well understood.

A recent study involving 185 healthy adults between the age of 21 and 80 years, who underwent TCD and multimodal MRI, revealed that blood flow velocity decreases with age while the caliber of large vessels remains similar among age groups. These findings suggest that age-related decreases in CBFV and impaired CVR likely reflect small vessel diseases [13]. Another study further demonstrated that the speed of CVR of MCA response to induced vasodilation with CO2 slowed with age [14]. Further research is needed to gain a deeper understanding of the implications of CVR on treatment decisions and to determine optimal threshold values for CVR across all age groups, enabling informed therapeutic decisions.
