CT or MRI of the brain including CT or MR angiography of large intracranial arteries is necessary to rule out nonlacunar pathology. This should be done as an emergency in an acute stroke, particularly if there is any sign of clinical progression or fluctuation. CT scan is less sensitive than MRI scan for the smaller lacunes in the brainstem and thalamus. In acute settings, MRI-DWI sequence overestimates final infarct size. One third of lacunar infarcts will not result in a cavity (Koch 2011). The carotid arteries should be evaluated following a lacunar stroke with Doppler ultrasonography and MR angiogram. Those with moderate or greater stenosis of a symptomatic extracranial internal carotid artery should be considered for cerebral angiography and carotid endarterectomy. Transcranial Doppler ultrasonography is an alternative, noninvasive method of detecting intracranial vascular stenoses and is a useful test to evaluate the cerebral vascular reactivity, pulsatility index, and resistivity index as markers of intracranial large and small vessel occlusive disease. Clinical findings should be used to indicate the need for other tests. Although the transesophageal echocardiography has a well-established value in the investigation of the stroke mechanism, evidence suggests that the combination of a small subcortical infarction with a typical lacunar syndrome has a 100% negative predictive value for a cardioembolic source (Rabinstein et al 2006). Serum ischemia-modified albumin (IMA), used as a biomarker for acute coronary ischemia, has recently been identified as a useful biomarker of acute symptomatic lacunar infarcts, being more sensitive than homocysteine (Ma 2011).