traumatic brain injury associated diffuse axonal injury

Current Trends in the Current Trends in the Imaging of Diffuse Imaging of Diffuse

Axonal InjuryAxonal InjuryEdwin Chu, MS IVEdwin Chu, MS IV

University of Texas Medical School in San AntonioUniversity of Texas Medical School in San AntonioGillian Lieberman, MD Gillian Lieberman, MD

Harvard Medical SchoolHarvard Medical SchoolBeth Israel Deaconess Medical CenterBeth Israel Deaconess Medical Center

Edwin Chu, MS IVEdwin Chu, MS IV

Gillian Lieberman, MDGillian Lieberman, MD

September 2009September 2009

OutlineOutline

Introduction to Traumatic Brain InjuryIntroduction to Traumatic Brain Injury

Our Patient: MCOur Patient: MC

Diffuse Axonal Injury (DAI)Diffuse Axonal Injury (DAI)

Imaging Modalities for Diffuse Axonal InjuryImaging Modalities for Diffuse Axonal Injury

SummarySummary

AcknowledgementsAcknowledgements

ReferencesReferences



Introduction to Traumatic Brain Introduction to Traumatic Brain Injury (TBI)Injury (TBI)

Defined as damage to the brain from an external Defined as damage to the brain from an external mechanical force. mechanical force.

Examples of such forces include rapid Examples of such forces include rapid acceleration or deceleration motions, impact acceleration or deceleration motions, impact injuries, or penetration by a projectile injuries, or penetration by a projectile

Incidence: 200Incidence: 200--225/100,000 225/100,000

12% of all U.S. hospital admissions are TBI12% of all U.S. hospital admissions are TBI--

relatedrelated

Meythaler, J. M. (2001). "Current concepts: diffuse axonal injury-associated traumatic brain injury." Archives of physical medicine and rehabilitation

82(10): 1461-71.



Our Patient: MCOur Patient: MC

CC: Traumatic Brain InjuryCC: Traumatic Brain Injury

HPI: 23 HPI: 23 y/oy/o

M with unknown medical history M with unknown medical history transferred from an outside hospital transferred from an outside hospital s/ps/p

high speed high speed

(~100mph) motorcycle vs. bus accident. Pt was (~100mph) motorcycle vs. bus accident. Pt was helmeted. In the field, GCS 3. Negative helmeted. In the field, GCS 3. Negative toxtox

screen.screen.

GCSGCS--

Glasgow Coma ScoreGlasgow Coma Score



On AdmissionOn Admission--

Patient MC: CT ImagingPatient MC: CT Imaging


Gillian Lieberman, MDGillian Lieberman, MDImages from PACS, BIDMC

Axial non contrast CT imaging showing Axial non contrast CT imaging showing hyperdensityhyperdensity

(green box) in left frontal lobe (green box) in left frontal lobe consistent with a hemorrhagic contusion. No consistent with a hemorrhagic contusion. No other signs of hemorrhage were seen acutely.other signs of hemorrhage were seen acutely.

3 Days Later3 Days Later--

Patient MC : MRI T2 FlairPatient MC : MRI T2 Flair

Images from PACS, BIDMC



Axial T2 weighted Flair MR imaging Axial T2 weighted Flair MR imaging showing showing hyperintensehyperintense

signal in the right signal in the right and left greyand left grey--white matter interface and white matter interface and spleniumsplenium

of the corpus of the corpus callosumcallosum

Axial T2 weighted Flair MR Imaging Axial T2 weighted Flair MR Imaging showing showing hyperintensehyperintense

signalsignal

in the right in the right posterior limb of the internal capsule posterior limb of the internal capsule and a left frontal lobe contusionand a left frontal lobe contusion

Areas of Hemorrhage


Patient MC : MRI T2 FlairPatient MC : MRI T2 Flair



Axial T2 weighted Flair MR imaging Axial T2 weighted Flair MR imaging showing showing hyperintensehyperintense

signal in the signal in the corpus corpus callosumcallosum


Patient MC : MR Patient MC : MR Susceptibility Weighted ImagingSusceptibility Weighted Imaging



Axial SW MR imaging showing Axial SW MR imaging showing hypohypo--intense signal in the right and intense signal in the right and left greyleft grey--white matter interface and a white matter interface and a left frontal lobe contusionleft frontal lobe contusion

Axial SW MR imaging showing hypoAxial SW MR imaging showing hypo--

intense lesions in the right greyintense lesions in the right grey--white white matter interface and matter interface and spleniumsplenium; left ; left frontal lobe contusionfrontal lobe contusion

Areas of Hemorrhage


Patient MC : MR Patient MC : MR Susceptibility Weighted ImagingSusceptibility Weighted Imaging



Axial T2 weighted SW MR imaging Axial T2 weighted SW MR imaging showing hyposhowing hypo--intense signal in the intense signal in the corpus corpus callosumcallosum

Axial T2 weighted SW MR imaging Axial T2 weighted SW MR imaging showing hyposhowing hypo--intense signal in the intense signal in the corpus corpus callosumcallosum

Diffuse Axonal InjuryDiffuse Axonal Injury

Biomechanics, Pathogenesis, Stages of Biomechanics, Pathogenesis, Stages of Damage, and LongDamage, and Long--term Consequencesterm Consequences

Diffuse Axonal Injury (DAI)Diffuse Axonal Injury (DAI)

Severe head trauma can produce diffuse axonal Severe head trauma can produce diffuse axonal injury characterized by injury characterized by punctatepunctate

hemorrhagic or hemorrhagic or

nonnon--hemorrhagic lesions primarily in white matter hemorrhagic lesions primarily in white matter tracts tracts

Common sites: Common sites: ParasagittalParasagittal

white matter, greywhite matter, grey--white white matter junctions of the cerebral cortex, corpus matter junctions of the cerebral cortex, corpus callosum, and brainstemcallosum, and brainstem

Occurs in 40Occurs in 40--50% of patients hospitalized for TBI50% of patients hospitalized for TBI

Affects more than 2 million people every yearAffects more than 2 million people every yearEdwin Chu, MS IVEdwin Chu, MS IV

Gillian Lieberman, MDGillian Lieberman, MDMeythaler, J. M. (2001). "Current concepts: diffuse axonal injury-associated traumatic brain injury." Archives of physical medicine and rehabilitation

82(10): 1461-71.

DAI and its LongDAI and its Long--Term Term ConsequencesConsequences

26,000 deaths/yr are due to DAI26,000 deaths/yr are due to DAI

20,00020,000--

45,000 surviving patients/yr suffer 45,000 surviving patients/yr suffer

neurobehavioral or physical impairmentsneurobehavioral or physical impairments

Average hospital cost per patient: $117,000Average hospital cost per patient: $117,000

Direct health care costs: $25 billion/yearDirect health care costs: $25 billion/year


Gillian Lieberman, MDGillian Lieberman, MDMeythaler, J. M. (2001). "Current concepts: diffuse axonal injury-associated traumatic brain injury." Archives of physical medicine and rehabilitation

82(10): 1461-71.

Biomechanics of DAIBiomechanics of DAI

Commonly referred to as a shear force injuryCommonly referred to as a shear force injury

Rapid head motions produce inertial forces Rapid head motions produce inertial forces which cause rotational acceleration of the brain which cause rotational acceleration of the brain leading to shearing and strain of axons leading to shearing and strain of axons

Rapid stretch of an axon leads to damage to the Rapid stretch of an axon leads to damage to the neuronneuron’’s cytoskeleton. Axonal transport s cytoskeleton. Axonal transport continues until local inflammation causes further continues until local inflammation causes further cytoskeleton breakdowncytoskeleton breakdown



Pathogenesis of Microscopic Axonal Pathogenesis of Microscopic Axonal ChangesChanges

Increased cytoskeleton Increased cytoskeleton damage + protein damage + protein accumulation = axon accumulation = axon disconnectiondisconnection

Axon disconnection Axon disconnection leads to irreversible leads to irreversible damagedamage

Pathologic Feature: Bulb Pathologic Feature: Bulb formationformation

Brain InjuryBrain Injury

Influx of NaInflux of Na++ and Caand Ca2+2+ through through respective channelsrespective channels

Axonal SwellingAxonal Swelling

Axonal cytoskeleton damageAxonal cytoskeleton damage

Accumulation of axonal transport Accumulation of axonal transport proteins within swellingsproteins within swellings Edwin Chu, MS IVEdwin Chu, MS IV


Histopathology of DAIHistopathology of DAI

Top: Low power view of Top: Low power view of hematoxylinhematoxylin--

eosin stain demonstrating DAI and eosin stain demonstrating DAI and petechialpetechial

hemorrhageshemorrhages

Below: Silver stain of the same area Below: Silver stain of the same area indicating the axonal terminal bulbs.indicating the axonal terminal bulbs.

Images from: Meythaler, J. M. (2001). "Current concepts: diffuse axonal injury-associated traumatic brain injury." Archives of physical medicine and rehabilitation

82(10): 1461-71.



Stages of DAIStages of DAI

StageStage Areas AffectedAreas Affected

II -- parasagittalparasagittal

regions of the frontal lobesregions of the frontal lobes

-- periventricularperiventricular

temporal lobes temporal lobes

-- internal and external capsules internal and external capsules

-- cerebellumcerebellum

IIII Stage I areas + corpus Stage I areas + corpus callosumcallosum

IIIIII Stage I + Stage II areas + Stage I + Stage II areas + dorsolateraldorsolateral

quadrants of the quadrants of the rostralrostral

brain stembrain stem

Adams, J. H. (1989). "Diffuse axonal injury in head injury: definition, diagnosis and grading." Histopathology

15(1): 49-59.



Imaging Modalities for Diffuse Imaging Modalities for Diffuse Axonal InjuryAxonal Injury



Imaging of DAI: CTImaging of DAI: CT

CT imaging is first line for any CT imaging is first line for any neurotraumaneurotrauma

BenefitsBenefits

Widely available in most Widely available in most hospitals in the UShospitals in the US

Comparatively Comparatively inexpensiveinexpensive

Good, quick test for Good, quick test for injuries that require injuries that require immediate surgical immediate surgical attentionattention

DrawbacksDrawbacks

Initially 50Initially 50--80% of pts 80% of pts with DAI will have with DAI will have normal CT scansnormal CT scans

Less sensitivity for Less sensitivity for detecting DAIdetecting DAI

Toyama, Y. (2005). "CT for acute stage of closed head injury." Radiation medicine

23(5): 309-16.



Examples of DAI on CT Imaging: Examples of DAI on CT Imaging: Companion Patient TCCompanion Patient TC

HPI: 22 HPI: 22 y/oy/o

F being found down in the road,F being found down in the road,

entangled with her bicycle, unresponsive, entangled with her bicycle, unresponsive, unhelmetedunhelmeted, pupils, pupils

unequal. Initial CGS was 4 unequal. Initial CGS was 4

upon arrival to ED. upon arrival to ED.



Companion Patient TC: Companion Patient TC: Axial NonAxial Non--Contrast CT ImagingContrast CT Imaging



Areas of Hemorrhage

Soft Tissue Edema

Companion Patient TC: Companion Patient TC: Axial NonAxial Non--Contrast CT ImagingContrast CT Imaging



Areas of Hemorrhage

More Examples: NonMore Examples: Non--Contrast CT Contrast CT Imaging showing Hemorrhagic DAI Imaging showing Hemorrhagic DAI

Lesions Lesions

Left Image from: Provenzale, J. (2007). "CT and MR imaging of acute cranial trauma." Emergency radiology

14(1): 1-12.

Right Image from: Toyama, Y. (2005). "CT for acute stage of closed head injury." Radiation medicine

23(5): 309-16.



Black arrows: areas of hemorrhagic foci

Imaging of DAI: MRIImaging of DAI: MRI

MRI has greater sensitivity in detecting DAIMRI has greater sensitivity in detecting DAI

Commonly used techniques include Flair, DWI, and Commonly used techniques include Flair, DWI, and GRE, and SWI* GRE, and SWI*

Kinoshita et al.Kinoshita et al.--

DWI sensitivity in detecting DAI is DWI sensitivity in detecting DAI is comparable to Flaircomparable to Flair

Tong et al.Tong et al.--

Number of hemorrhagic DAI lesions seen on Number of hemorrhagic DAI lesions seen on SWI was 6 times greater than that on conventional T2* SWI was 6 times greater than that on conventional T2* weighted 2D GRE imaging and the volume of hemorrhage weighted 2D GRE imaging and the volume of hemorrhage was approx 2 fold greaterwas approx 2 fold greater



* Flair* Flair--

Fluid Attenuated Inversion Recovery Fluid Attenuated Inversion Recovery DWIDWI--

Diffusion weighted ImagingDiffusion weighted ImagingGREGRE--

Gradient Recalled EchoGradient Recalled EchoSWISWI--

Susceptibility Weighted ImagingSusceptibility Weighted Imaging

T2 MR Imaging of DAIT2 MR Imaging of DAI

SagittalSagittal

T2T2--weighted MR image showing hyperweighted MR image showing hyper--intense intense signal within the corpus signal within the corpus callosumcallosum

(white arrows)(white arrows)

Image from: Provenzale, J. (2007). "CT and MR imaging of acute cranial trauma." Emergency radiology

14(1): 1-12.



MR FLAIR image showing hyper-intense lesion in the left splenium

Images from: Kinoshita, T. (2005). "Conspicuity of diffuse axonal injury lesions on diffusion-

weighted MR imaging." European journal of radiology

56(1): 5-11.

MR Flair: Conspicuity of DAI MR Flair: Conspicuity of DAI LesionsLesions



MR FLAIR image showing hyper-intense lesion in the left frontal grey-white matter interface

MR DWI: Conspicuity of DAI MR DWI: Conspicuity of DAI LesionsLesions

Images from: Kinoshita, T. (2005). "Conspicuity of diffuse axonal injury lesions on diffusion-

weighted MR imaging." European journal of radiology

56(1): 5-11.



MR DWI–Gx

image showing high-intensity lesion in the splenium

MR DWI–Gz

image showing high-

intensity lesion in the left frontal grey-white matter interface

More Lesions are seen on More Lesions are seen on Susceptibility Imaging: Comparing Susceptibility Imaging: Comparing

T2 and SWI T2 and SWI

A)A)

Axial T2 MRIAxial T2 MRI

B)B)

Axial SusceptibilityAxial Susceptibility--weighted MRIweighted MRI

Small hemorrhagic shearing injuries in Small hemorrhagic shearing injuries in the left frontal the left frontal subcorticalsubcortical

white matter white matter

(Black arrows)(Black arrows)

Image from: Tong, K. A., S. Ashwal, et al. (2008). "Susceptibility-weighted MR imaging: a review of clinical applications in children." AJNR. American journal of neuroradiology

29(1): 9-17.



More Lesions are seen on More Lesions are seen on Susceptibility Imaging: Comparing Susceptibility Imaging: Comparing

T2 and SWIT2 and SWI

C) Axial T2 MRIC) Axial T2 MRI

D) Axial SusceptibilityD) Axial Susceptibility--weighted weighted MRIMRI

Hemorrhagic shearing foci Hemorrhagic shearing foci ((open arrowsopen arrows) in the left frontal ) in the left frontal white matter, right white matter, right subinsularsubinsular

region, and left region, and left spleniumsplenium

Image from: Tong, K. A., S. Ashwal, et al. (2008). "Susceptibility-weighted MR imaging: a review of clinical applications in children." AJNR. American journal of neuroradiology

29(1): 9-17.



The Emergence of MRI Diffusion The Emergence of MRI Diffusion Tensor Tensor TractographyTractography

(DTT)(DTT)

DTT is rapidly becoming another modality to DTT is rapidly becoming another modality to look for DAI in the acute phaselook for DAI in the acute phase

Modality can characterize white matter integrity Modality can characterize white matter integrity by measuring fractional anisotropy (FA)by measuring fractional anisotropy (FA)

Fractional anisotropy is the degree of alignment Fractional anisotropy is the degree of alignment of the underlying nerve fibers (ratio: 0 to 1) of the underlying nerve fibers (ratio: 0 to 1)

Wang, J. Y., B. Khamid, et al. (2008). "Diffusion tensor tractography

of traumatic diffuse axonal injury." Archives of neurology

65(5): 619-26.



Using DTT for LongUsing DTT for Long--Term DAI Term DAI FollowFollow--upup

SkoglundSkoglund

et al.et al.

22 22 y/oy/o

F with closed head injury. Comparison F with closed head injury. Comparison images of Axial T2 and DTT at 6 days postimages of Axial T2 and DTT at 6 days post--injury injury and 18 months postand 18 months post--injuryinjury

Results: In followResults: In follow--up imaging, conventional MRI up imaging, conventional MRI showed no pathology. However, in DTT imaging, showed no pathology. However, in DTT imaging, FA values had improved but did not normalize.FA values had improved but did not normalize.

Conclusion: MRConclusion: MR--DTT may be more sensitive to DTT may be more sensitive to DAI than conventional MR imaging. DAI than conventional MR imaging.

Skoglund, T. S. (2008). "Long-term follow-up of a patient with traumatic brain injury using diffusion tensor imaging." Acta

radiologica

(Stockholm, Sweden : 1987)

49(1): 98-100.



Results: LongResults: Long--Term DAI FollowTerm DAI Follow--up up with DTTwith DTT

a) 6 days post injurya) 6 days post injury--

Axial Axial T2 MR image showing T2 MR image showing hyperhyper--intense lesion in left intense lesion in left ponspons

b) 18 months post injuryb) 18 months post injury-- Axial T2 MR image showing Axial T2 MR image showing

no lesionno lesion

c) 6 days post injuryc) 6 days post injury--

Axial Axial DTT image showing DTT image showing decreased blue intensitydecreased blue intensity

d) 18 months post injuryd) 18 months post injury-- Axial DTT image showing Axial DTT image showing

moderately improved blue moderately improved blue intensityintensity

Images from: Skoglund, T. S. (2008). "Long-term follow-up of a patient with traumatic brain injury using diffusion tensor imaging." Acta

radiologica


49(1): 98-100.



Fractional Anisotropy in LongFractional Anisotropy in Long--Term Term DAI FollowDAI Follow--upup

FA values on left side FA values on left side improve 18 months postimprove 18 months post--

injury but do not injury but do not normalize to rightnormalize to right--sided sided valuesvalues

Key:Key:

dxdx

––

PatientPatient’’s right sides right side

sin sin ––

PatientPatient’’s left sides left side

Graph from: Skoglund, T. S. (2008). "Long-term follow-up of a patient with traumatic brain injury using diffusion tensor imaging." Acta

radiologica


49(1): 98-100.



SummarySummary

Diffuse Axonal Injury is caused by traumatic brain Diffuse Axonal Injury is caused by traumatic brain injury and can be characterized by injury and can be characterized by punctatepunctate

hemorrhagic or nonhemorrhagic or non--hemorrhagic lesions primarily hemorrhagic lesions primarily in white matter tracts in white matter tracts

MRI is now the imaging of choice for detecting MRI is now the imaging of choice for detecting DAI. SWI and DWI are the best techniquesDAI. SWI and DWI are the best techniques

DTT holds promising results as an imaging DTT holds promising results as an imaging modality for the acute and longmodality for the acute and long--term followterm follow--up of up of DAI patientsDAI patients



AcknowledgementsAcknowledgements

Special thanks to Dr. Special thanks to Dr. RafeequeRafeeque

BhadeliaBhadelia

for help for help

with this index case and presentationwith this index case and presentation

Dr. Dr. RivkaRivka

ColenColen

Dr. Gillian Dr. Gillian LierbermanLierberman



ReferencesReferences

Adams, J. H. (1989). "Diffuse axonal injury in head injury: definition, diagnosis and grading." Histopathology

15(1): 49-59.Kinoshita, T. (2005). "Conspicuity of diffuse axonal injury lesions on diffusion-weighted MR

imaging." European journal of radiology

56(1): 5-11.Meythaler, J. M. (2001). "Current concepts: diffuse axonal injury-associated traumatic brain injury."

Archives of physical medicine and rehabilitation

82(10): 1461-71.Provenzale, J. (2007). "CT and MR imaging of acute cranial trauma." Emergency radiology

14(1): 1-12.

Skoglund, T. S. (2008). "Long-term follow-up of a patient with traumatic brain injury using diffusion tensor imaging." Acta

radiologica


49(1): 98-100.

Smith, D. H. (2003). "Diffuse axonal injury in head trauma." The Journal of head trauma rehabilitation

18(4): 307-16.

Tong, K. A., S. Ashwal, et al. (2008). "Susceptibility-weighted MR imaging: a review of clinical applications in children." AJNR. American journal of neuroradiology

29(1): 9-17.Toyama, Y. (2005). "CT for acute stage of closed head injury." Radiation medicine

23(5): 309-16.

Wang, J. Y., B. Khamid, et al. (2008). "Diffusion tensor tractography

of traumatic diffuse axonal injury." Archives of neurology

65(5): 619-26.



traumatic brain injury associated diffuse axonal injury

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