The brain can be injured in various ways. Traumatic brain injury (TBI) refers specifically to physical trauma, directly or indirectly, to the head causing brain injury due to physical forces imparted to the brain. Traumatic brain injuries are classified relative to the causative factors, such as penetrating, direct blunt force or indirectly as in rapid head movement without direct blunt force applied to the head (e.g., whiplash). TBIs are also classified based on the severity of neurological impairment and the duration of any loss of consciousness. As a result, traumatic brain injuries are classified as mild, moderate or severe. A “concussion” is a form of mild TBI. Both the neurological sequalae and the appearance on neuroimaging can be highly variable, depending on what portion of the brain is injured. Naturally, these numerous variables which influence the outcome of any physically traumatic injury to the brain has made it difficult to research and validate methods of imaging TBI.
In 2014, there were approximately 2.87 million TBI-EDHDs (TBI-related Emergency Department Visits, Hospitalizations, and Deaths) in the U.S., including over 837,000 of these health events among children. The 2014 data represents a 53% increase from 2006, in which there were approximately 1.88 million TBI-EDHDs. A more complete estimate of the annual incidence of TBI is likely much higher because an unknown number of TBI and concussion incidents go unreported. Thus, the CDC has estimated that approximately 2 million people of all age groups in the UnitedStatesannually are affected by some form of TBI, and the global estimates is in the tens of millions. In the US, there were about 61,000 TBI-related deaths in 2019.
Although the vast majority of TBI incidents are of the mild to moderate level, but even at these 2 levels short- and long-term brain dysfunction health problems can be associated with significant life-affecting health problems.Unfortunately, in its mild to moderate forms, TBI can be an elusive diagnosis to make as its most common presentations include non-specific symptoms such as: headache, dizziness, inability to concentrate, memory problems and light and sound sensitivity.
As such, mild to moderate levelTBIsarea diagnostic challenge. The usual anatomic brain imaging methods of MRI and CT usually show no brain structural abnormalities. As a result, the clinical opinion of the so-called “normal” anatomical MRI or CT is that no significant short- or longer-term brain dysfunction injury is present in the symptomatic individual. When functional neuroimaging is utilized, a different story emerges.
Over the last 30 years, SPECT brain function imaging has been shown to be more sensitive than either CT or MRI because it shows brain functional impairments rather than structural abnormalities.
SPECTbrain function imaging has consistently shown perfusion/function abnormalities in traumatic brain injury despite normal morphology, and results are considered to have a prognostic value for persistence of neuropsychological sequelae [63-72]
A 2014 systematic review by Raji and colleagues [2] showed Level IIA evidence for the utility of brain SPECT in the evaluation of TBI. The review identified 52 cross sectional studies and 19 longitudinal studies with a total of 2,634 individuals over 30 years of literature supporting this conclusion.
SPECT brain perfusion/function imaging proved more sensitive than CT or MRI [3-9]. Jacobs and colleagues followed a group of patients with TBI who had SPECT scans within three weeks of injury. They found an abnormal baseline SPECT had a sensitivity of 100% and specificity of 85% for predicting persistent neuropsychological deficits at 12 months, while a negative baseline SPECT had a negative predictive value of 100% for neuropsychological deficits at 6 and 12 months after injury.
In total, 18 cross sectional studies showed correlation between abnormal SPECT findings and neuropsychological deficits [2]. This suggests that abnormalities found with brain SPECT can correlate with and, therefore, be predictive of functional outcomes.
Those outcomes include distinguishing between TBI and PTSD. A retrospective study of over 20,000 subjects showed that SPECT can distinguish TBI from PTSD with 80-100% sensitivity and an average of 70% specificity [71]. Replication of this study in a smaller sample of 196 military veterans with TBI, PTSD, or both showed accuracy of between 83% and 94% in distinguishing between these conditions [5, 10].
In 2021, the Canadian Association of Nuclear Medicine (CANM) published procedure guidelines on the use of perfusion SPECT. The guidelines cite that TBI is a clear indication for the use of perfusion SPECT neuroimaging [11].
A common location for SPECT brain abnormalities is in the temporal lobes. The image on the viewer’s left shows a focally decreased cortical tracer uptake in the anterior medial left frontal lobe (expected normal cortical tracer uptake appearance is seen in the image on the viewer’s right). Image courtesy of Yin-Hui Siow.
Another common location for brain SPECT abnormalities is in the inferior frontal lobes. The image on the viewer’s left shows a focally decreased cortical tracer uptake in the inferior frontal lobes bilaterally. (expected normal cortical tracer uptake appearance along with overall bilateral brain cortical tracer uptake is seen in the image on the viewer’s right)
Most people of all agesare simply not aware of how easily the brain’s function can become impaired even with seemingly minorevents not involving direct impact of the head, such as occurs with acceleration injury (e.g., whiplash). Thus, many patients incur repetitive, seemingly minor, TBIs over the course of years before their cumulative brain dysfunctional signs and symptoms become apparent to them or those around them. By then,their SPECT brain function scan can show extensive focally impaired sites throughout their brain.
Multiple bilateral focal perfusion deficits can be observed on typical cross-sectional images but can be more readily observed on 3D Cortical Perfusion images format.
20-year-old female SPECT brain function selected cross-sectional images.
Same 20-year-old female SPECT brain function 3D Cortical Perfusion map. Expected range of cerebral uptake is depicted in the yellow coloring (indicated by the red arrow in the right-sided color scale). Multiple, bilateral brain regions of diminished function are colored in the dark green and blue coloring, such as the bilateral temporal lobes (red thin arrows) and the bilateral posterior parietal cortices (yellow hollow arrows). Vertical white arrows point to the lateral ventricles (not brain tissue).
Same 20-year-old female SPECT brain function Population Database Comparison Map. Statistical parametric comparison of patient’s perfusion to the age-matched normative database indicated by the horizontal gray arrows on right-side color scale.Multiple, bilateral areas of decreased perfusion are shown in green (-2 s.d. to -2.99 s.d.), light blue (-3 s.d. to -3.99 s.d.), dark blue (-4 s.d. to -4.99 s.d.) and black (-5 s.d. or worse). Vertical white arrows point to the lateral ventricles.
TRAUMATIC BRAIN INJURY
1. Newberg AB, Alavi A. Neuroimaging in patients with head injury. Semin Nucl Med 2003;33:136–47.
2. Raji CA, Tarzwell R, Pavel D, et al. Clinical utility of SPECT neuroimaging in the diagnosis and treatment of traumatic brain injury: a systematic review. PLoS One 2014;9(3):e91088. Doi:10.1371/journal.pone.0091088.
3. Abdel-Dayem HM, Abu-Judeh H, Kumar M, et al. SPECT brain perfusion abnormalities in mild or moderate traumatic brain injury. Clin Nucl Med 1998;23(5):309–17.
4. Abu-Judeh HH, Parker R, Aleksic S, et al. SPECT brain perfusion findings in mild or moderate traumatic brain injury. Nucl Med Rev Cent East Eur 2000;3(1):5–11.
5. Shin YB, Kim S-J, Kim I-J, et al. Voxel-based statistical analysis of cerebral blood flow using Tc-99m ECD brain SPECT in patients with traumatic brain injury: group and individual analyses. Brain Inj 2006;20(6):661–7.
6. Stamatakis EA,Wilson JT, Hadley DM, et al. SPECT imaging in head injury interpreted with statistical parametric mapping. Journel of Nuclear Medicine, 2002 43(4):476-83.
7. Jacobs A, Put E, Ingels M, Bossuyt A. Prospective evaluation of technetium-99m-HMPAO SPECT in mild and moderate traumatic brain injury. J Nucl Med. 1994 Jun;35(6):942-7.
8. Jacobs A, Put E, Ingels M, et al. One-year follow-up of technetium-99m-HMPAO SPECT in mild head injury. J Nucl Med 1996;37(10):1605–9.
9. Amen DG, Raji CA, Willeumier K, et al. Functional Neuroimaging Distinguishes Posttraumatic Stress Disorder from Traumatic Brain Injury in Focused and Large Community Datasets. PLoS One 2015;10(7):e0129659. Doi: 10.1371/journal.pone.0129659.
10. Raji CA, Willeumier K, Taylor D, et al. Functional neuroimaging with default mode network regions distinguishes PTSD from TBI in a military veteran population. Brain Imaging Behav 2015;9(3):527–34. Doi: 10.1007/s11682-015-9385-5.
11. Cohen PF, Tarzwell R, Numerow L, et al., CANM guidelines for brain perfusion single photon emission computed tomography (SPECT). 2021. https://www.canm-acmn.ca/guidelines.
Head Trauma
The brain can be injured in various ways. Traumatic brain injury (TBI) refers specifically to physical trauma, directly or indirectly, to the head causing brain injury due to physical forces imparted to the brain. Traumatic brain injuries are classified relative to the causative factors, such as penetrating, direct blunt force or indirectly as in rapid head movement without direct blunt force applied to the head (e.g., whiplash). TBIs are also classified based on the severity of neurological impairment and the duration of any loss of consciousness. As a result, traumatic brain injuries are classified as mild, moderate or severe. A “concussion” is a form of mild TBI. Both the neurological sequalae and the appearance on neuroimaging can be highly variable, depending on what portion of the brain is injured. Naturally, these numerous variables which influence the outcome of any physically traumatic injury to the brain has made it difficult to research and validate methods of imaging TBI.
In 2014, there were approximately 2.87 million TBI-EDHDs (TBI-related Emergency Department Visits, Hospitalizations, and Deaths) in the U.S., including over 837,000 of these health events among children. The 2014 data represents a 53% increase from 2006, in which there were approximately 1.88 million TBI-EDHDs. A more complete estimate of the annual incidence of TBI is likely much higher because an unknown number of TBI and concussion incidents go unreported. Thus, the CDC has estimated that approximately 2 million people of all age groups in the UnitedStatesannually are affected by some form of TBI, and the global estimates is in the tens of millions. In the US, there were about 61,000 TBI-related deaths in 2019.
Although the vast majority of TBI incidents are of the mild to moderate level, but even at these 2 levels short- and long-term brain dysfunction health problems can be associated with significant life-affecting health problems.Unfortunately, in its mild to moderate forms, TBI can be an elusive diagnosis to make as its most common presentations include non-specific symptoms such as: headache, dizziness, inability to concentrate, memory problems and light and sound sensitivity.
As such, mild to moderate levelTBIsarea diagnostic challenge. The usual anatomic brain imaging methods of MRI and CT usually show no brain structural abnormalities. As a result, the clinical opinion of the so-called “normal” anatomical MRI or CT is that no significant short- or longer-term brain dysfunction injury is present in the symptomatic individual. When functional neuroimaging is utilized, a different story emerges.
Over the last 30 years, SPECT brain function imaging has been shown to be more sensitive than either CT or MRI because it shows brain functional impairments rather than structural abnormalities.
SPECTbrain function imaging has consistently shown perfusion/function abnormalities in traumatic brain injury despite normal morphology, and results are considered to have a prognostic value for persistence of neuropsychological sequelae [63-72]
A 2014 systematic review by Raji and colleagues [2] showed Level IIA evidence for the utility of brain SPECT in the evaluation of TBI. The review identified 52 cross sectional studies and 19 longitudinal studies with a total of 2,634 individuals over 30 years of literature supporting this conclusion.
SPECT brain perfusion/function imaging proved more sensitive than CT or MRI [3-9]. Jacobs and colleagues followed a group of patients with TBI who had SPECT scans within three weeks of injury. They found an abnormal baseline SPECT had a sensitivity of 100% and specificity of 85% for predicting persistent neuropsychological deficits at 12 months, while a negative baseline SPECT had a negative predictive value of 100% for neuropsychological deficits at 6 and 12 months after injury.
In total, 18 cross sectional studies showed correlation between abnormal SPECT findings and neuropsychological deficits [2]. This suggests that abnormalities found with brain SPECT can correlate with and, therefore, be predictive of functional outcomes.
Those outcomes include distinguishing between TBI and PTSD. A retrospective study of over 20,000 subjects showed that SPECT can distinguish TBI from PTSD with 80-100% sensitivity and an average of 70% specificity [71]. Replication of this study in a smaller sample of 196 military veterans with TBI, PTSD, or both showed accuracy of between 83% and 94% in distinguishing between these conditions [5, 10].
In 2021, the Canadian Association of Nuclear Medicine (CANM) published procedure guidelines on the use of perfusion SPECT. The guidelines cite that TBI is a clear indication for the use of perfusion SPECT neuroimaging [11].
A common location for SPECT brain abnormalities is in the temporal lobes. The image on the viewer’s left shows a focally decreased cortical tracer uptake in the anterior medial left frontal lobe (expected normal cortical tracer uptake appearance is seen in the image on the viewer’s right). Image courtesy of Yin-Hui Siow.
Another common location for brain SPECT abnormalities is in the inferior frontal lobes. The image on the viewer’s left shows a focally decreased cortical tracer uptake in the inferior frontal lobes bilaterally. (expected normal cortical tracer uptake appearance along with overall bilateral brain cortical tracer uptake is seen in the image on the viewer’s right)
Most people of all agesare simply not aware of how easily the brain’s function can become impaired even with seemingly minorevents not involving direct impact of the head, such as occurs with acceleration injury (e.g., whiplash). Thus, many patients incur repetitive, seemingly minor, TBIs over the course of years before their cumulative brain dysfunctional signs and symptoms become apparent to them or those around them. By then,their SPECT brain function scan can show extensive focally impaired sites throughout their brain.
Multiple bilateral focal perfusion deficits can be observed on typical cross-sectional images but can be more readily observed on 3D Cortical Perfusion images format.
20-year-old female SPECT brain function selected cross-sectional images.
Same 20-year-old female SPECT brain function 3D Cortical Perfusion map. Expected range of cerebral uptake is depicted in the yellow coloring (indicated by the red arrow in the right-sided color scale). Multiple, bilateral brain regions of diminished function are colored in the dark green and blue coloring, such as the bilateral temporal lobes (red thin arrows) and the bilateral posterior parietal cortices (yellow hollow arrows). Vertical white arrows point to the lateral ventricles (not brain tissue).
Same 20-year-old female SPECT brain function Population Database Comparison Map. Statistical parametric comparison of patient’s perfusion to the age-matched normative database indicated by the horizontal gray arrows on right-side color scale.Multiple, bilateral areas of decreased perfusion are shown in green (-2 s.d. to -2.99 s.d.), light blue (-3 s.d. to -3.99 s.d.), dark blue (-4 s.d. to -4.99 s.d.) and black (-5 s.d. or worse). Vertical white arrows point to the lateral ventricles.
TRAUMATIC BRAIN INJURY
1. Newberg AB, Alavi A. Neuroimaging in patients with head injury. Semin Nucl Med 2003;33:136–47.
2. Raji CA, Tarzwell R, Pavel D, et al. Clinical utility of SPECT neuroimaging in the diagnosis and treatment of traumatic brain injury: a systematic review. PLoS One 2014;9(3):e91088. Doi:10.1371/journal.pone.0091088.
3. Abdel-Dayem HM, Abu-Judeh H, Kumar M, et al. SPECT brain perfusion abnormalities in mild or moderate traumatic brain injury. Clin Nucl Med 1998;23(5):309–17.
4. Abu-Judeh HH, Parker R, Aleksic S, et al. SPECT brain perfusion findings in mild or moderate traumatic brain injury. Nucl Med Rev Cent East Eur 2000;3(1):5–11.
5. Shin YB, Kim S-J, Kim I-J, et al. Voxel-based statistical analysis of cerebral blood flow using Tc-99m ECD brain SPECT in patients with traumatic brain injury: group and individual analyses. Brain Inj 2006;20(6):661–7.
6. Stamatakis EA,Wilson JT, Hadley DM, et al. SPECT imaging in head injury interpreted with statistical parametric mapping. Journel of Nuclear Medicine, 2002 43(4):476-83.
7. Jacobs A, Put E, Ingels M, Bossuyt A. Prospective evaluation of technetium-99m-HMPAO SPECT in mild and moderate traumatic brain injury. J Nucl Med. 1994 Jun;35(6):942-7.
8. Jacobs A, Put E, Ingels M, et al. One-year follow-up of technetium-99m-HMPAO SPECT in mild head injury. J Nucl Med 1996;37(10):1605–9.
9. Amen DG, Raji CA, Willeumier K, et al. Functional Neuroimaging Distinguishes Posttraumatic Stress Disorder from Traumatic Brain Injury in Focused and Large Community Datasets. PLoS One 2015;10(7):e0129659. Doi: 10.1371/journal.pone.0129659.
10. Raji CA, Willeumier K, Taylor D, et al. Functional neuroimaging with default mode network regions distinguishes PTSD from TBI in a military veteran population. Brain Imaging Behav 2015;9(3):527–34. Doi: 10.1007/s11682-015-9385-5.
11. Cohen PF, Tarzwell R, Numerow L, et al., CANM guidelines for brain perfusion single photon emission computed tomography (SPECT). 2021. https://www.canm-acmn.ca/guidelines.