Detecting the basis of cognitive dysfunction in mild Traumatic Brain Injury
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Detecting the basis of cognitive
dysfunction in mild TBI:
The role of quantitative MRI
Andrew M. Blamire
Newcastle MR Centre & Institute of Cellular Medicine
Newcastle University
Context - Prognostic Indicators in TBI
• Moderate/severe TBI account for ~10% of all cases
– Prognostic calculators
• CRASH1 - mortality at 14 days
• IMPACT2 - severe disability at 6 months
• Mild TBI : remaining ~90% of all cases
– Prolonged cognitive deficits in 15 - 45% of mild TBI3
– No prognostic calculator
Treatments in mild TBI – limited
(1) Perel P, et al. BMJ. 336(7641):425-9, (2008).
(2) Lingsma HF, et al. Lancet Neurology. 9(5):543-54 (2010).
(3) Thornhill, S., Teasdale, G.M., et al. BMJ. 320, 1631-1635 (2000).
Context - Conventional MRI Disconnection between imaging and clinical assessment
• Out-patients (scanned 4-7 days)
GCS 13
No LoC,
PTA 4 hrs
(M33PG)
GCS 13
No LoC
PTA 12 hrs
(M34GR)
GCS 13
LoC 5 mins
PTA 30 mins
(M16KW)
GCS 14
LoC 2 mins
PTA 12 hours
(M24HM)
GCS 9
LoC 10 mins
PTA 10 days
(H09ET)
GCS 7
LoC 5 mins
PTA 1hr
(H08MM)
Mild TBI Moderate TBI
Context - Conventional MRI Disconnection between imaging and clinical assessment
• Out-patients (scanned 4-7 days)
GCS 13
No LoC,
PTA 4 hrs
(M33PG)
GCS 13
No LoC
PTA 12 hrs
(M34GR)
GCS 13
LoC 5 mins
PTA 30 mins
(M16KW)
GCS 14
LoC 2 mins
PTA 12 hours
(M24HM)
GCS 9
LoC 10 mins
PTA 10 days
(H09ET)
GCS 7
LoC 5 mins
PTA 1hr
(H08MM)
Mild TBI Moderate TBI
Key Questions
1. Can advanced MRI methods identify markers of
acute tissue injury?
2. Do such imaging markers provide a neurobiological
basis for cognitive dysfunction following mild TBI?
3. Do any MRI measures have prognostic value?
Comprehensive imaging battery
Prospective, longitudinal study
mild TBI
Key Questions
1. Can advanced MRI methods identify markers of
acute tissue injury?
2. Do such imaging markers provide a neurobiological
basis for cognitive dysfunction following mild TBI?
3. Do any MRI measures have prognostic value?
Comprehensive imaging battery
Prospective, longitudinal study
mild TBI
Improving Structural Imaging Quantitative T1 Relaxometry
Conventional T1w - qualitative
2.0s 0.5s
Quantitative T1 map 200
400
600
T1 (s)
Pix
els
0.6 0.8 1 0
Evidence of acute cortical injury Regional qT1 Abnormalities
• Brain “parcellated” into 8 regions / hemisphere
– Visible lesions excluded
Significant GM changes in T1 1.100
1.150
1.200
1.250
1.300
1.350
1.400
1.450
1.500
1.550
1.600
Rig
ht
Occ
ipit
al-P
arie
tal G
rey
Mat
ter
T1 (
s)
Control
Mild
Moderate
ANOVA p<<0.001
21/53 outside normal range
Pathophysiology of TBI Diffuse Axonal Injury (DAI)
Compression
Tension
Shearing
Shearing
Disruption of axoplasmic flow
Extrusion of axoplasm & organelles
Microtubule Damage & Disassembly
Axonal bulbs
Tang-Schomer et al, FASEBJ, 24: 1401-1410 (2010)
Assessing Axonal Damage Diffusion Tensor Imaging (DTI)
Fractional
Anisotropy
(FA)
Mean
Diffusivity
(MD)
DTI contrast based on diffusion restriction
Evidence of acute white matter injury TBSS - Groupwise Patients vs Control
53 TBI, 33 Controls, p<0.05, Croall et al, Neurology in press 2014
0 20 40 Z =
MD
Water diffusibility is increased Structural damage
Evidence of acute white matter injury TBSS - Groupwise Patients vs Control
53 TBI, 33 Controls, p<0.05, Croall et al, Neurology in press 2014
Motion is more ordered
Diffusibility is increased along these WM tracts
FA
0 20 40 Z =
Key Questions
1. Can advanced MRI methods identify markers of
acute tissue injury?
2. Do such imaging markers provide a neurobiological
basis for cognitive dysfunction following mild TBI?
3. Do any MRI measures have prognostic value?
Comprehensive imaging battery applied in a
prospective, longitudinal imaging study in mild TBI
Cortical damage & cognitive dysfunction
• Significant correlations between VLF performance and
left hemisphere cortical regions
Relationship between
cortical (GM) T1 and VLF performance score
(Controlled for NART)
1000
1100
1200
1300
1400
1500
1600
0 10 20 30 40 50 60
Le
ft T
em
pe
ro-P
ari
eta
l G
rey
Ma
tte
r T
1(m
s)
VLF Score (Corrected for NART)
R2=0.142, p<0.01
1000
1100
1200
1300
1400
1500
1600
0 10 20 30 40 50 60
Le
ft T
em
pe
ro-P
ari
eta
l G
rey
Ma
tte
r T
1 (
ms
)
VLF Score (Corrected for NART
Controls
WM damage & cognitive dysfunction Regression analysis against Verbal Fluency
• Worse cognitive performance relates to elevated FA
Groupwise
FA Increased
Negative
FA regression to
verbal fluency
0
10
20
30
40
50
60
70
0.30 0.35 0.40 0.45 0.50
Ve
rbal
Flu
en
cy S
core
Fractional Anisotropy
Croall et al, Neurology in press 2014
Key Questions
1. Can advanced MRI methods identify markers of
acute tissue injury?
2. Do such imaging markers provide a neurobiological
basis for cognitive dysfunction following mild TBI?
3. Do any MRI measures have prognostic value?
Comprehensive imaging battery applied in a
prospective, longitudinal imaging study in mild TBI
Relationship to Outcome
• Rivermead Post Concussion Questionnaire • Nausea, Fatigue, Concentration, Depression, Headache, etc
• Assessed as outcome at 12 months (n=37/53)
n=30 n=22 n=15
1180
1200
1220
1240
1260
1280
1300
1320
1340
Control 0 or 1 symptom 2 or more symptoms
p<0.02
p<0.005
Wh
ole
Gre
y M
att
er
T1 (
ms)
AC
UT
E
Chronic RPCQ
Summary
• Acute, diffuse cortical and white matter injury detectable by
quantitative MRI approaches
• Mild TBI behaves differently to moderate/severe TBI
– Axonal compaction (FA) rather than destruction (FA)
• Strong relationship between cortical and WM damage and cognitive
performance
• Index of global cortical damage has prognostic value
Acknowledgements
Sir Jules Thorn Charitable Trust
Funding
MR Physics Jiaboa He
Benjamin Aribisala
Iain Croall
Radiographers Louise Morris
Carol Smith
Tim Hodgson
Tamsin Gaudie
Philips Medical Systems Matthew Clemence
Clinical Team - TBI Chris Cowie
Patrick Mitchell
David Mendelow
Psychology Tom Kelly
David Miller
Josh Wood
Anna Peel
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