Key words
brain death - brain perfusion - scintigraphy - quality control - CT angiography
Introduction
The fourth update of the guidelines regarding the determination of the irreversible
loss of total function of the cerebrum, the cerebellum, and the brain stem came into
effect on 7/6/2015 [1]. In compliance with the legal mandate according to § 16 Para. 1 Pg. 1 No. 1 of the
Transplantation Act, these guidelines define the current state of medical science
regarding the rules for determining death according to § 3 Para. 1 Pg. 1 No. 2 of
the Transplantation Act and the rules for determining the irreversible loss of total
function of the cerebrum, the cerebellum, and the brain stem according to § 3 Para.
2 No. 2 of the Transplantation Act including the required qualifications of physicians.
They replace the guidelines from 1998 [2]. Written statements from different professional associations including the German
Society of Neuroradiology (DGNR) and the German Society for Nuclear Medicine (DGN)
were taken into consideration. A clear change is the replacement of the previously
used term “brain death” with the more precise term “irreversible loss of brain function”.
An irreversible loss of brain function is usually the result of the cessation of cerebral
blood circulation. If the cessation of cerebral blood circulation is detected, potentially
reversible causes of clinical symptoms of loss of brain function are excluded. Therefore,
the irreversibility of a loss of brain function can be determined without a wait time
and follow-up clinical examinations. Methods such as Doppler/duplex ultrasound, perfusion
scintigraphy, and CT angiography are used for this purpose. As in the previous guidelines,
the indication for selective arterial angiography (DSA) requires the possibility of
therapeutic consequences.
This article is limited to the use of radiological and nuclear medicine imaging to
determine the presence of irreversible loss of brain function. Special diagnostic
features before and at the start of the third year of life are taken into consideration
in the guidelines.
Radiology
In addition to the description of the necessary qualifications of independent diagnosticians,
the approval of CT angiography (CTA) as a supplementary examination method is a major
innovation. As in the subsequently described nuclear medicine methods, use of CTA
in radiology and neuroradiology requires a standardized procedure with competent evaluation.
The pathophysiological basis of the cessation of cerebral blood circulation is an
increase in the intracranial pressure above the mean arterial pressure. Cerebral perfusion
then ceases so that the brain has an insufficient metabolic supply. Dupas et al. [3] studied and confirmed the reliability of CT angiography for determining the cessation
of cerebral blood circulation in a large study for the first time in 1998. Subsequently,
CTA was approved first in France and then in Canada, Austria, and additional countries
for the diagnosis of an irreversible loss of brain function ("brain death"). This
study and subsequent studies [4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14] were subjected to a Cochrane analysis in 2014 [15]. The sensitivity for detecting the cessation of cerebral blood circulation in the
case of a previous loss of brain function was 85 %. The main cause of the lack of
detection in 15 % of patients was traumatic or iatrogenic opening of the cranium that
prevented an increase in intracranial pressure above the mean arterial pressure. In
all examinations in which the cessation of cerebral blood circulation was documented
via CTA, the irreversible loss of total function of the cerebrum, the cerebellum,
and the brain stem was also confirmed.
Due to the significant success of interventional stroke therapy [16]
[17], CT angiography has been used nationwide in Germany in recent years to document
persistent vascular occlusions. This has resulted in a qualitatively and quantitatively
excellent foundation for the use of CT angiography. In contrast to a thrombotic occlusion
in the case of stroke, a pathological increase in intracranial pressure does not result
in a vascular occlusion. An increase in the time from intravenous contrast administration
results in relatively delayed spreading of the contrast agent in the intracranial
arteries, so-called "stasis filling". This very protracted spreading of contrast agent
has already been observed in the case of the use of conventional intracranial angiography
and must not be confused with perfusion. In addition, there are problems evaluating
CT angiography scans that additionally contain a "venous" acquisition series. Therefore,
as confirmed by studies by Welschehold et al. [14], it is recommended to restrict information to be diagnostically used to the arterial
phase in the case of this issue. In the case of contrast enhancement of the anterior
cerebral artery, middle cerebral artery, posterior cerebral artery and basilar artery,
the cessation of cerebral blood circulation is not definitively proven according to
the currently valid guidelines [1]. Another examination or a second clinical follow-up evaluation must then be performed
after the specified wait times.
The evaluation protocols used in the studies published to date regarding the detection
of the cessation of cerebral blood circulation differ significantly. Therefore, standardization
was required also in the above-mentioned Cochrane review [15]. Accordingly, a protocol for a standardized CTA procedure was created with the goal
of maximum safety. With respect to evaluation, a very conservative approach was selected
to ensure acceptance by requesting physicians and family members of patients [1]. The scan parameters listed in [Table 1] were defined in relation to the largest German study to date regarding the use of
CTA for determining the loss of brain functions [12]. The present CTA protocol must be observed exactly and must be evaluated by radiologists
with many years of experience in neuroradiology, ideally by radiologists specialized
in neuroradiology since the irreversible loss of total function of the cerebrum, the
cerebellum, and the brain stem is also present with the detection of the cessation
of cerebral blood circulation ([Fig. 1]). The evaluation of CTA scans can be very challenging in the case of subarachnoid
hemorrhage and venous stasis with simultaneous pronounced brain swelling. If the protocol
is followed precisely, it is possible for external specialists with the proper qualifications
to evaluate CT and CTA scans.
Table 1
The following protocol is validated and to be used for adults [1].
|
CTA protocol for evaluating the cessation of cerebral blood circulation
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|
requirements
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unenhanced CT
|
|
|
|
CT angiography
|
-
intravenous administration of 65 ml of contrast agent (highly concentrated) via pressure
infusion injection, followed by 30 ml of an isotonic saline solution, delivery rate
of 3.5 ml/sec; the start of the spiral scan of cervical vertebral body 6, scan to
the vertex is performed automatically via bolus tracking 5 seconds after at least
150 HU are achieved in the common carotid artery. 120 kV; 200 mA; table advance is:
4 cm/sec
|
|
|
|
findings in the case of the cessation of cerebral blood circulation
|
-
no contrast enhancement of the M1 segments of the middle cerebral artery, the A1 segments
of the anterior cerebral artery, the basilar artery, the P1 segments of the posterior
cerebral artery. Stasis filling can occur in V4 segments of the vertebral artery,
in the PICA (posterior inferior cerebral artery) and the distal internal carotid artery
(include in finding)
|
|
|
|
|
There is currently not sufficient literature regarding persons less than 18 years
of age.
Fig. 1 Arrest of cerebral blood circulation confirmed by CT angiography. Residual contrast
media inside the distal extradural internal carotid artery (ACI) (a), no contrast
media inside the intradural ACI (b, open arrow). The bilateral anterior cerebral artery,
middle cerebral artery, posterior cerebral artery and basilar artery showed no contrast
enhancement. In comparison, good contrast enhancement (arrows) of the bilateral superficial
temporal artery (quality control) is seen.
Nuclear medicine
The established procedure for performing perfusion scintigraphy in nuclear medicine
has not changed since 1988 [2]. The revised guidelines emphasize the qualification requirements for examining physicians
with respect to evaluation.
In perfusion scintigraphy, static scintigraphic images record the perfusion of brain
tissue via a hydrophilic tracer that is metabolically actively absorbed and bound
(trapped) over many hours in a virtually unchanged concentration. The lack of absorption
of the radiopharmaceutical cannot be due to medication or metabolism.
Radiopharmaceuticals whose diagnostic reliability has been validated, such as Tc-99m-ethyl
cysteinate dimer (ECD) and Tc-99m-hexamethylpropyleneamine oxime (HMPAO), must be
used. Sufficiently substantiated studies regarding the use of biomarkers used in positron
emission tomography are not currently available [19].
Different scintigraphic views must be documented. SPECT can also be performed. After
bolus injection of the radiopharmaceutical, the large cranial vessels are initially
visualized from a ventral direction and then static scintigraphy is performed to record
tissue perfusion.
Lateral projections are required to ensure the reliability of perfusion examinations
in the vertebrobasilar region. If there is still doubt due to overlapping of soft
tissue structures, superimposition-free visualization with SPECT is necessary.
The scintigraphic criteria of an irreversible loss of brain function are a lack of
visualization of cerebral vessels and cerebral perfusion and enhancement of the radiopharmaceutical
in the brain tissue [4]
[20]
[21]
[22]
[23]
[24]
[25]
[26].
Quality control should be performed in vitro by determining the labeling yield (ideally
greater than 90 %) via thin layer chromatography. In addition, the physiological distribution
of the radiopharmaceutical should be checked by scintigraphy of the thorax and abdomen
as an in vivo quality control.
Perfusion scintigraphy must be monitored and evaluated by a nuclear medicine specialist.
