The Use Of Nuclear Medicine In Determining Brain Death
Brain death is an irreversible loss of brain function that results in permanent adverse effects on various important functions of the body. (Kowalsky, 2013) A diagnosis of brain death is widely accepted to be comparable to legal death, even though it is not universally accepted. (Young, 2018) Brain death can be caused a variety of events from head trauma, severe hypoxia, and stroke. (Kowalsky, 2013) These events generally result in the build-up of fluid in the skull, increasing pressure and interrupting blood flow to the brain. (Kowalsky, 2013)
The use of nuclear medicine to determine brain death is important to provide key diagnostic information that cannot be found using more conventional computer tomography (CT) and magnetic resonance imaging (MRI) scans. (Mettler & Guiberteau, 2012) (Kowalsky, 2013) Planar brain imaging, single photon emission computer tomography (SPECT) and positron emission tomography (PET) scans can provide further information on suspected abnormalities in the cerebrum, cerebral blood flow and the movement of the cerebrospinal fluid (CSF) in the confirmation of brain death. (Mettler & Guiberteau, 2012)
The physical principles behind NM imaging
Radiopharmaceuticals
A range of radiopharmaceuticals are used for brain imaging, and depending on the modality chosen and region of interest, specific tracers may be more ideal over others. (Mettler & Guiberteau, 2012) Planar brain imaging uses perfusion agents, SPECT brain perfusion imaging use lipophilic radiopharmaceuticals that constantly cross the blood-brain barrier to localise in the normal brain tissue, and PET metabolic brain imaging which uses positron-emitting radiopharmaceuticals. (Mettler & Guiberteau, 2012) Radiopharmaceuticals can be separated into two groups; lipophilic and hydrophilic. Lipophilic tracers are able to cross the normal blood-brain barrier and localise in normal brain cells. (Kowalsky, 2013) Hydrophilic tracers will cross the abnormal blood-brain barrier and only localise in pathology within the brain. (Kowalsky, 2013) Another method of classifying brain radiopharmaceuticals is identifying their metabolic characteristics. (Kowalsky, 2013) There are those that bind to protein after an intravenous injection, distribute extracellularly and localize intracellularly. The perfect radiopharmaceutical for brain imaging is easily prepared and safe to administer, practical prices, less than twenty-four hours half-life, producing monenergistic gamma rays and focused target towards lesions. (Kowalsky, 2013)
Planar brain imaging
Planar brain imaging is also known as a static image as the radiopharmaceutical has localised and settled into a stationary position, and only used in brain death imaging. (Kowalsky, 2013) It is usually acquired from four projections; posterior, anterior, left lateral and right lateral, with the anterior view being acquired with the head in flexion to provide a clearer frontal image. (Kowalsky, 2013) Planar brain imaging typically use short lasting perfusion agent’s technetium-99m (99mTc), diethylenetriamine pentaacetic acid (DTPA) [Tc-DTPA], and lipophilic perfusion agents 99mTc-pertechnetate, 99mTc-hexamethylpropyleneamine oxime (HMPAO) and 99mTc-ethylene 1-cysteinate dimer (ECD). (Mettler & Guiberteau, 2012) HMPAO and ECD are often used in more difficult cases to reveal further brain activity and are extracted from the brain after its first cycle. (Mettler & Guiberteau, 2012) In brain death cases, the radioactive tracer travels through the carotid artery until it halts at the base of the skull due to the elevated pressure within the skull.
If there is a lack of flow inside the cerebrum, brain death is the likely cause. (Mettler & Guiberteau, 2012) A lateral or anterior cerebral view is usually acquired to determine any existence of activity in the sagittal sinus. (Mettler & Guiberteau, 2012) Activity in the sagittal sinus may indicate a slight intracerebral flow, although it will not reject a diagnosis of brain death. (Mettler & Guiberteau, 2012)
The hot-nose sign is an indirect sign of brain death, and although it does not hold any real diagnostic value, it is a useful secondary indication. (Huang, 2005) The cessation of internal carotid artery flow will increase the flow into the maxillary branch of the external carotid artery displaying increased perfusion over the nasal area. (Huang, 2005)SPECTSPECT imaging is recognized to be a valuable resource in locating lesions in the brain as its better definition helps separate superficial lesions from deeper lesions. (Kowalsky, 2013) SPECT usually requires the acquisition of 64 projections done in a full 360 degree rotation around the patient. After the collection of projection data and rotations of the gamma cameras, the transverse images are reconstructed to form a 3-dimensional image of the patient volume. (Kowalsky, 2013)
In a SPECT image, the passage of fluid through the brain should be compared with the other hemisphere of the brain inside the cortical gray matter. (Mettler & Guiberteau, 2012) An increase or decrease of perfusion will indicate a pathological process change in the same local area of the contralateral hemisphere of the brain. (Mettler & Guiberteau, 2012) A fusion CT or MRI scan with a SPECT image can often assist in adding detail to the pathologic process visualised. (Mettler & Guiberteau, 2012) SPECT brain imaging uses several groups or lipophilic radiopharmaceuticals that are able to cross the blood-brain barrier. They are retained in the brain and are able to travel with the regional cerebral blood flow and therefore map the distribution of brain perfusion in brain tissue. There are two main radiopharmaceuticals used in brain death imaging; 99mTc-HMPAO (exametazime) and 99mTc-ECD (bicisate). (Mettler & Guiberteau, 2012) Absence of perfusion and lack of cerebral activity on the SPECT image will confirm brain death. HMPAO in SPECT is the most common method of radionuclide modality due to its ability to cross the blood-brain barrier. (Young, 2018) Once it enters the tissues in the brain, it metabolises into a hydrophilic form where it is retained. (Mettler & Guiberteau, 2012) ECD has similar properties to HMPAO, however it is removed from the blood at a faster rate to reduce background activity, and is more stable with a postpreperation shelf life of 6 hours. (Mettler & Guiberteau, 2012) (Kowalsky, 2013)
The safety aspects of using radioactive materials
Radioactive materials are tightly controlled and regulated as unsafe use may expose patients, radiation workers and the public to unnecessary external radiation leading to deterministic and stochastic side effects. (Radiation Health and Safety Advisory Council, 2008) There are multiple safety equipment and standards radiation workers are required to follow and use in order to achieve the as low as reasonably achievable (ALARA) process; a complete safety principle to minimise radiation dose and release of radioactive materials. (Radiation Health and Safety Advisory Council, 2008) There are three key principles that ALARA and radiation safety can utilize; length of time exposed to ionising radiation, distance from ionising radiation sources and utilization of shielding. (PerkinElmer, 2007)
Time
Any exposure to radiation can be harmful to the human body. Although the risk is extremely miniscule with smaller amounts of low-level radiation, the length of time exposed to a radioactive material will accumulate radiation dosage. (International Atomic Energy Agency, 2014) Time spent around radioactive materials should be minimised to follow the as low as reasonably achievable principle. (IAEA, 2014)Time can be decreased through a variety of methods before the operation occurs as well as during the operation. (PerkinElmer, 2007)
Going through the procedure and reviewing safety details before the operation will help gain experience, enabling the operation to be done as quickly as possible. (Radiation Health and Safety Advisory Council, 2008) Handling radioactive sources like preparing, dispensing and administrating will reduce time required with practice. (Radiation Health and Safety Advisory Council, 2008) All equipment should be adjusted or constructed before the introduction of the radioactive source. (PerkinElmer, 2007) During the operation, paperwork, discussions, questions, instructions or other activities irrelevant to the procedure should be conducted outside the radiation areas. (PerkinElmer, 2007) Irradiated equipment should also be taken off as soon as possible and monitored to ensure minimal exposure. (PerkinElmer, 2007) DistanceKeeping distance away from radiation sources is extremely important to lower dose rate. (IAEA, 2014)
Radiation follows the inverse square law, which for example, if the distance from the source is doubled, the dose rate will be a quarter of the original distance. (PerkinElmer, 2007) This means the dose rate will increase exponentially the smaller the distance to source. (PerkinElmer, 2007) When dealing with patients with an internal radiopharmaceutical, attempt to stay at least 1m away during short visits. (Radiation Health and Safety Advisory Council, 2008) In longer visits of over 2 hours, a 2 metre distance should be kept and minimized close contact (pregnant women or children should be discouraged to visit. (Radiation Health and Safety Advisory Council, 2008)There are several methods to ensure maximum distance is kept from the radioactive material. Direct handling should be avoided, and shielding must be used. (PerkinElmer, 2007) Tongs, forceps and other equipment should be used to maximise distance from the hand and the radiation worker. (Radiation Health and Safety Advisory Council, 2008) Sources should also be stored far away in the back with ventilation that cannot be accessed normally. (PerkinElmer, 2007)
Shielding
There are many different types of shielding that should be utilized to ensure minimal exposure to radiation. (IAEA, 2014) Nuclear medicine typically use gamma rays for imaging and therapeutic purposes which required heavier metals such as lead or tungsten. (Radiation Health and Safety Advisory Council, 2008) Protective equipment can include syringe shields, lead walls, lead windows, lead doors, shielded containers and hot lab dispensing areas. (Radiation Health and Safety Advisory Council, 2008) Other methods of decreasing exposure to radiation using shielding materials include calculating shielding requirements before the operation, placing concrete blocks around radioactive storage areas and employing mirrors and periscopes to avoid direct line of sight. (PerkinElmer, 2007)Syringe shields are the first layer or protection against radiation to be used whenever possible. (IAEA, 1990) They are made with either tungsten or lead and is used as a sleeve around the syringe. (PerkinElmer, 2007) It will reduce the percentage of dose to the hand, eye and gonads down to 4 percent against 99mTc radiopharmaceuticals. (IAEA, 1990) Dispensing and withdrawing radionuclide solutions should be prepared behind a lead glass using shielded syringes. (IAEA, 2014) Concrete or lead blocks may also be used to offer further protection. (IAEA, 2014)
Protective aprons, gloves and other organ shields should be employed as appropriate to the operation. Lead aprons may be 0. 5 mm to 1mm thick. (IAEA, 1990) They will not reduce any dosage to the hands or eyes, although the dosage to the gonads will be 36 percent of the original dose. (IAEA, 1990) Lead aprons should not be utilized as the only method of protection, however when using a syringe shield, the dose to the gonads will be reduced from 4 percent to 1 percent. (IAEA, 1990) Likewise, leaded gloves do not provide any significant radiation by itself, although the dose rate reaching the hands will be reduced from 4 percent to 1 percent when using a syringe shield. (IAEA, 1990)
Eye glasses will reduce the dose percentage to the eye by 77 precent, and this will be improved to 99 percent when using a syringe shield compared to 96 percent with just the syringe shield. (IAEA, 1990) Dose limitThe occupational dose limit from the Australia Radiation Protection and Nuclear Safety Agency (ARPANSA) is an effective dose from ionizing radiation of 20 millisieverts per year, averaged over 5 years without exceeding 50 millisieverts in any one year. (ARPANSA 2014) An equivalent dose delivered to the lens of the eye should be under 20 millisieverts per year, averaged over 5 years. The hands, feet and skin have an equivalent dose limit of 500 millisieverts every year. (ARPANSA 2014) The occupational dose limit is much lower than the threshold of detrimental health effects. (Radiation Health and Safety Advisory Council, 2008)
The occupational dose limits are justified by the benefits they provide compared to the low risk of radiation exposure. (PerkinElmer, 2007) All radiation workers however should be monitored to ensure that the dose limit is not breached. (PerkinElmer, 2007)Radioactive monitoring Geiger counters are highly sensitive radioactive measuring devices. (PerkinElmer, 2007) They are used to check for contamination on equipment like gloves after reconstituting, dispensing and administrating radiopharmaceuticals. (Radiation Health and Safety Advisory Council, 2008) They should also be utilized to check lab dispensing areas for contamination before use. (Radiation Health and Safety Advisory Council, 2008)Personal Radioactive monitors should be provided to all personnel in nuclear medicine centres who are likely to receive an annual dose of over 1 millisievert. (Radiation Health and Safety Advisory Council, 2008)
The most common dosimeter is the thermoluminescent dosimeter (TLD) that stores radiation as energy, and is released as light when heated. (PerkinElmer, 2007) The amount of light will be directly proportional to the amount of radiation dosage received. (PerkinElmer, 2007) Other dosimeters include optically stimulated luminescent dosimeters (OSLD) and pocket ionization chamber (PIC). (PerkinElmer, 2007) Personal dosimeters are required to be carried on the part of the body that is most likely to receive the largest dose. (PerkinElmer, 2007)
Basic clinical applications of NMIndication/Contra-indications
Most of nuclear medicine brain scans are without risk and contra-indications. (Tam, 2015) Indications for nuclear Planar brain imaging and SPECT is currently preferred over contrast angiography due to it being a less invasive procedure with less risks involved. (Kowalsky, 2013) Computer tomographic angiographs are another alternative to nuclear medicine that is fast and efficient found in most hospitals. (Berenguer, Davis & Howington, 2010)
Brain Death Studies
The timeline of a brain death study is as follows:
- The imaging room is prepared for a patient on life support
- Dynamic flow images are captured for 2 minutes
- Statics are captured (anterior and posterior skull view and bilateral skull view)
- SPECT or SPECT/CT is performed
The scan is begun and tracer is immediately injected as an intravenous bolus injection with rapid flush in proximal vein or central line. Flow images (fast 1-second frame images) are acquired for 2 minutes. The flow images should start before the arrival of the bolus in the neck and end well after the venous phase. Three-minute anterior and posterior skull view and bilateral skull views are then acquired. In potential organ donors, additional views of the anterior and posterior kidney, lung, and liver are acquired. SPECT or SPECT/CT can be performed as an additional view to confirm perfusion status in the brain.
