Measurement of Blood Flow

Possible mechanisms for brain death include an obstruction of circulation by cerebral swelling. The demonstration of absent intracranial circulation indicates irreversible

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Angiography

Contrast Angiography

Absence of blood flow to the brain leads to destruction of brain tissue. The greatest advantage of angiography for the determination of brain death is that it is influenced neither by CNS-depressant drugs nor by hypothermia. This method has been recommended to confirm brain death.^{[30] [101] [109] [110]} "Practice Parameters for Determining Brain Death in Adults" recommended conventional angiography as a confirmatory test, and the following criteria were identified:^[10] There should be no intracerebral filling at the level of the carotid bifurcation or circle of Willis; the external carotid circulation is patent; and filling of the superior longitudinal sinus may be delayed. Drawbacks of this method are that the patients need to be transported to the radiology suite, and the cost is relatively high. Intra-arterial (aortic arch) or intravenous (vena cava) digital subtraction angiography (DSA) has been shown to be as effective as conventional four-vessel angiography, is less invasive, and is easier to perform.^{[101] [109] [111] [112]}

Radionuclide Angiography

Confirmation of brain death using conventional dynamic radionuclide angiography with blood pool agents has been used for a long time.^{[113] [114]} Such investigations are less invasive than others and may be carried out at the bedside using a mobile scintillation camera. Radioligands such as technetium 99m (^99m Tc) hexamethyl-propyleneamine-oxime (HMPAO) and N-isopropyl-p-¹²³ I-iodoamphetamine (IMP), which cross the blood-brain barrier and are picked up and held by viable cells for several hours, are recommended to confirm brain death.^{[115] [116] [117]} The lack of uptake of isotope in brain parenchyma (i.e., hollow skull phenomenon) is characteristic for brain death.^[10] These tests can be of value for patients who have no viable neurons despite preserved brain perfusion resulting from artifactual cerebral perfusion pressure or whose perfusion scans are inconclusive. ^99m Tc-HMPAO is also used for tomographic functional imaging (single photon emission computed tomography [SPECT]) to confirm the diagnosis of brain death, which allows much more precise regional information.^{[118] [119] [120] [121]}

Computed Tomography

Dynamic computed tomography (CT) has been useful as a nonivasive test to confirm brain death.^{[122] [123]} After intravenous bolus injection of iodinated contrast media, time-density analysis of a specific area can be obtained with a CT scanner equipped with a special software program that can evaluate blood flow. This technique also has the advantage of demonstrating underlying intracranial disorders that may cause coma. Xenon-CT cerebral blood flow techniques have been applied to a wide variety of clinical problems, including the confirmation of brain death.^{[30] [124] [125] [126]} This technique is accurate in quantifying low cerebral blood flow, and the information can be directly correlated with CT anatomy. Pistoria and associates^[125] suggested that an average global flow of less than 5 mL/100 mL/min confirms brain death.

Magnetic Resonance

Magnetic resonance (MR) imaging (MRI) and MR angiography have been used for the confirmation of brain death with the advent of MRI-compatible ventilators. ^{[127] [128] [129] [130] [131]} MRI allows an assessment of intracranial contents and is particularly helpful in defining abnormalities in the posterior fossa, which may be obscured by bone artifact inherent in CT. Phosphorus (³¹ P) and proton (¹ H) MR spectroscopy (MRS) methods also have been used for the determination of brain death.^{[132] [133] [134] [135]} MRS can demonstrate the total absence of high-energy phosphorus compound (including ATP), leaving only one single peak of inorganic phosphate in ³¹ P MRS and massive lactate concentration in ¹ H MRS. However, this technique unfortunately lacks information on regional brain conditions. Diffusion-weighed MRI, which detects the molecular diffusion of water, is used for the diagnosis of a brain-dead patient. It can display anatomic changes associated with severe brain damage and can demonstrate ultrastructural changes resulting from brain death and differentiate them from edematous changes seen on conventional T2-weighted images.^[136]

Transcranial Doppler Sonography

TCD uses a 2-MHz ultrasonic probe affixed to the temporal area above the zygomatic arch, and the flow velocity of middle cerebral artery usually is monitored. However, it can also insonate the anterior cerebral artery and the posterior cerebral artery from the temporal window, the basilar and vertebral arteries from the occipital window, and the intracranial internal carotid artery and the ophthalmic arteries through the orbital window. It is noninvasive and inexpensive, and it can be performed at the patient's bedside without known risk to the patient. With increased intracranial pressure, mean flow velocity decreases, and the pulsatility index ([peak velocity-end-diastolic velocity]/mean velocity) increases.^[137] When intracranial pressure reaches levels approaching the mean arterial pressure (i.e., brain death), TCD demonstrates systolic spikes, undetectable flow (i.e., no signal), or reversal of blood flow in diastole (i.e., to-and-fro or oscillating waveform). ^{[138] [139] [140]} Feri and colleagues^[139] reported that these patterns were highly specific (100%) for brain death. Petty and coworkers^[140] also reported that these patterns were highly specific (100%) and sensitive (91.3%) for brain death. However, Paolin and associates^[30] think that a finding of "no signal" cannot be considered an expression of circulatory arrest unless it is confirmed by cerebral angiography or is the end point of deteriorating intracranial hemodynamics in patients submitted to serial TCD investigations. These TCD signals should be recorded from multiple intracranial arteries (both middle cerebral arteries or at least one middle cerebral artery and basilar artery) to be considered confirmatory of brain death without any other test to rule out the possibility of the occlusion of a single artery.^[140]

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Positron Emission Tomography

Positron emission tomography (PET) imaging involves intravenous injection of radiotracers labeled with positron-emitting nuclides (e.g., oxygen 15 [¹⁵ O], carbon 11 [¹¹ C], nitrogen 13 [¹³ N]). These radionuclides are incorporated into organic compounds that are chemically similar to those present in the body, and several physiologic parameters can be measured. A few of the reports about the use of PET in the setting of brain death indicated the utility of PET in the confirmation of brain death. No detectable glucose metabolism was reported using fluorine 18 fluorodeoxyglucose (¹⁸ F-FDG) in brain-dead patients.^{[141] [142]} However, the presence of cerebral blood flow and cerebral glucose metabolism was reported in brain-dead children. Medlock and colleagues^[143] reported a clinically brain-dead, 2-month-old infant with no cerebral electrical activity who demonstrated the persistence of glucose metabolism. These investigators speculated that the preservation of glucose metabolism was partly caused by glial cells, which are more resilient than neurons. The use of PET in the investigation of comatose or brain-dead patients is still in an early stage of development and limited by its high cost and need for special facilities. However, the capability of PET to accurately measure diverse physiologic parameters makes it a potentially powerful method for diagnosing brain-dead patients.