Future Tools for Diagnosis and Monitoring mTBI

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Future Tools for Diagnosis and Monitoring mTBI

• Maheen M. Adamson, PhD
• WRIISC Palo Alto VAHCS

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Outline

• TBI vs. mTBI
• Dissecting the injury
• Differences in structural MRI
• Why is standard clinical intervention not enough?
• Different types of neuroimaging that show
  promise.

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Definition of mild TBI - review

• Loss of consciousness (LOC) duration is
  relatively short less than 1 minute versus less
  than 10 minutes vs less than 30 minutes
• Post-traumatic amnesia (PTA) less than 24 hours
• Glasgow Coma Scale (GCS) 13-15 (acutely)
• No penetrating brain injury
• No focal neurological findings
• (different groups use different definitions)

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Complicated Mild TBI

• When clinical neuroimaging findings are present
  following a mTBI, the classification changes to
  complicated mTBI, which has a 6-month outcome
  more similar to moderate TBI1,2
• 1Williams DH, Levin HS, Eisenberg HM. Mild head
  injury classification. Neurosurgery
  199027(3)422-8.
• 2Kashluba S, Hanks RA, Casey JE, Millis SR.
  Neuropsychologic and functional outcome after
  complicated mild traumatic brain injury. Arch
  Phys Med Rehabil 2008 89(5) 904-11.

From Belanger, 2009
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What are the injuries?

• Most Common Primary Injuries
• Concussion (shaking of the brain caused by any
  violent blow the head, usually causing loss of
  consciousness)
• Contusion (bruising)
• Subdural hematoma (a bleed immediately under the
  dura)
• Diffuse axonal injury
• Most Common Secondary Injuries
• Excitotoxicity (release of calcium, binding of
  magnesium)
• Edema
• Ischemia

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Every Traumatic Brain Injury is Unique
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Severity of TBI Cases Treated at DVBIC Sites
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Military Issues regarding TBI

• Soldiers in Iraq are being exposed to a large
  number of blasts (IEDs), many soldiers exposed at
  the same time
• Some soldiers are exposed to many blasts
• Soldiers wear body armor that protects vital
  organs
• Helmets protect against missile injuries, but not
  against blast shock waves.
• It is difficult to identify the brain changes
  with mild TBI
• Consequently, many soldiers are getting brain
  damage and experiencing functional deficits
  attributable to TBI

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What are the forces?
Rotational force vector
Translational force vector
(Figure adapted from Arciniegas and Beresford
2001)
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TBI Pathology / Mechanisms

• Coup-contra-coup contusion
• Collision of medial temporal lobe structures,
  orbito-frontal cortex with bones of base of skull
• Breakage of blood vessels
• Macro hemorrhages - injury to large blood vessels
• Subdural hematoma local pressure
• Epidural hematoma arterial pressure, rapidly
  progressing
• Subarachnoid bleeding herniation normal
  pressure hydrocephalus
• Small hemorrhages arterioles (30-150 um)
• Microbleeds at the gray-white matter junction
• Disruption of blood flow, clotting
• Local edema, increased intracranial pressure
• Shear injury - breakage of axons (0.2 0.5 um)
• Vulnerability at gray-white matter junctions (Not
  Diffuse??)

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The Mechanisms of Damage from TBI
ICP Intracranial pressure CPP Cerebral
perfusion pressure SDH Sub Dural Hematoma DAI
Diffuse Axonal Injury
Courtesy Dr. Gary Abrams
Maas et al, Lancet Neurology, 2008
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Complex Interactions of Trauma Sequelae
Courtesy Dr. Gary Abrams
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Frontal and temporal pole contusions in two cases
as reported by Gurdjian (1975). Note the
extensiveness of the ventral surface contusions.
From Impact head injury Mechanistic, clinical
and preventive correlation (pp. 242, 243), by E.
S. Gurdjian, 1975, Springfield, IL Charles C.
Thomas.
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Parasagittal plane through the long axis of the
hippocampus at post-mortem. Note how the temporal
pole is cradled and hugged by the middle
cranial fossa as well as the sharp edge of the
sphenoid ridge, asit juts into the Sylvian
fissure. The head of hippocampus is approximately
2 cm from the sphenoid ridge and, when brain
compression occurs, can deform over the ridge.
From Atlas of the Human Brain (2nd ed., p. 83),
by J. K. Mai, G. Paxinos, and J. K. Assheuer,
2004, Amsterdam Elsevier.
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Coronal views are presented on top from an older
teenage patient who sustained a severe
traumatic brain injury (TBI). As visualized, the
fornix has withered in comparison to the
age-matched control. This is thought to represent
downstream degeneration of this structure as a
result of the hippocampal and medial temporal
lobe damage, including temporal horn dilation,
that can be seen on the right in comparison with
the control subject, where the true inversion
recovery sequence MRI scan provides exquisite
anatomical detail of the brain. Also, note the
marked reduction in the size of the temporal stem
and overall reduction in the amount and integrity
of the temporal lobe white matter in comparison
to the control.
Adapted from Bigler, 2007
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A patient who sustained a head injury from a
fall, where the focal impact was to the back of
the patients head, with the resulting contra
coup injury to fronto-temporal regions. Axial CT
toward the base of the skull depicting acute
inferior frontal and anterior temporal lobe
contusions, with associated edema. Note the close
proximity of the contusions to the sphenoid.
Adapted from Bigler, 2007
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3-D spiral CT coregistered with 3-D thin-slice MRI
A middle-aged individual who sustained a
significant temporal lobe contusion as a
consequence of a high speed, side-impact MVA.
This patient did sustain a significant left
temporal lobe contusion, where the follow-up MRI
approximately 2 years post-injury demonstrates
significant temporal horn dilation, hippocampal
atrophy (compare left and right hippocampal
size), and general volume loss of the temporal
lobe.
Adapted from Bigler, 2007
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Note variations in Location Volume Depth
Bigler, Neuropsychology, 2007
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What does the future hold?

• Arterial Spin Labeling Perfusion (clinical and
  research applications)
• Susceptibility weighted imaging (enhanced
  contrast magnitude image which is exquisitely
  sensitive to venous blood, hemorrhage and iron
  storage)
• Functional MRI (functional correlate of
  cognition)
• Resting states of the brain

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Arterial spin labeling perfusion

• Group activation maps obtained during letter
  2-back working memory task from control subjects
  (left)and patients with traumatic brain injury
  studied following either placebo (middle) or
  methylphenidate (MPH) (right). Frontal activation
  in patients is reduced on placebo when compared
  with activation in controls, but normal-appearing
  activation is restored after MPH administration.
  Source Unpublished data courtesy of Junghoon Kim
  and John Whyte, Moss Rehabilitation Institute.

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Susceptibility Weighted Imaging (SWI)

• Regions of venous vascular content and
  hemorrhage in a tumor, which are not seen in the
  conventional postcontrast T1-weighted image
  (left) (Sehgal et al., 2005).

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Functional MRI
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Working Memory in mTBI
McAllister et al., 2001
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Longitudinal Functional MRI in Severe TBI

• Increased activation observed after 6-month
  evolution in TBI patients during the 3-back
  condition.
• The most striking changes were seen in the
  bilateral prefrontal cortex, with left hemisphere
  predominance.
• The second region that showed statistical
  significant changes was the bilateral parietal
  posterior region.
• Both regions are involved in working memory
  processes. Statistical Parametric Maps with left
  as left.

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Kim et al., 2009
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Conventional MRI and resting-state fMRI
correlation analysis in a 21-year-old with verbal
memory deficits following traumatic brain injury
(A) Conventional MRI (FLAIR) revealed bilateral
superior frontal lesions but no abnormalities
that would explain the patients verbal memory
deficit (left to right transverse slices at the
level of hippocampus, thalamus, fornix,
cingulum).
MacDonald et al., 2008
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Resting state fMRI
Spatial map of resting BOLD correlations with the
left hippocampus. Yellow arrows indicate absence
of significant correlations between the left
hippocampus and anterior cingulate or between
left hippocampus and anterior thalamus. White
arrows point to areas of abnormally increased
correlation with the left hippocampus, of unknown
importance. (C) Normal right hippocampal
functional connectivity. Top panel BOLD signal
time course in the right hippocampus (green
line) and anterior cingulate (blue line) were
normally correlated (r 0.40). Bottom panel
spatial map of resting BOLD correlations with
right hippocampus. Significant correlations were
observed between the right hippocampus and
anterior cingulate as well as anterior thalamus
(yellow arrows). Images displayed in anatomic
space patients left side on the left side
of the images.
MacDonald et al., 2008
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Conclusions

• High resolution MRI
• PET Amyloid imaging
• Separating PTSD from TBI
• Understanding the long term effects of mTBI in
  OEF/OIF population in the context of neural,
  behavior and cognitive changes