Novel Proof of Concept to Assess Multifocal Neuronal Disease in … · 2018. 6. 25. · White Matter Tracts • Altered by neurodegenerative disorders, medications, or neuropsychological

Novel Proof of Concept to Assess Multifocal Neuronal Disease in Individuals

Using MRI

Abby Hentel

White Matter Tracts

• Altered by neurodegenerative disorders, medications, or neuropsychological conditions(Croteau-Chonka, et al. 2015)

• $1.5 trillion of U.S. Economy annually (Thakur, et al. 2016)

• Traumatic Brain Injury (TBI) • 30% all injury deaths• 2013- 50,000 deaths• (Wintermark, et al. 2015)

Introduction Methods Results Discussion References

http://www.cannabisoils.ca/wp-content/uploads/2014/11/neurodegenerative-diseases.jpg

http://www.tbibraininjurysurvivor.com/what-is-tbi/

2

Traumatic Axonal Injury

https://www.lyslaw.com/Spine-Injury-Traumatic-Brain-Injury-Support/Two-Primary-Types-Brain-Injuries.aspx


3

Problem with TBI• Mild Traumatic Brain Injury

(mTBI) – 80% all TBI• Does not typically show up

on conventional imaging


http://blog.cincinnatichildrens.org/wp-content/uploads/2015/08/CTandMR_head_blog20150805C.jpg

4

Solution: DTI• Diffusion Tensor Imaging (DTI)

• Extremely sensitive to changes in white matter microstructure (Jones, et al. 2010) (Lerner, et al. 2013)

• How does this work?• Measures diffusion of water molecules

throughout white matter tracts • Quantitatively analyzed

• Fractional Anisotropy (FA)

Introduction Methods Results Discussion Bibliography

5

Limitations of Quantitative DTI

• Assessment of data • Control group• Same hardware, parameters, software• Demographics• Impossible/Costly• No clinical usage

• Clinically used for visualization


6

Clinically used for visualization

Normal Brain Tumor

Tract Visualization with DTI

Normal Brain Tumor

Objective

3 scanners should show

same deviations

Quantify homogeneity of

each tract

Individual assessment

7


Data Collection

Anonymized normative database

under medical college IRB

Subjects agreed to have MRI/DTI scan up to 3 different scanners•33 Direction GE DTI•55 Direction GE DTI•64 Direction Siemens DTI

All subjects had no history of brain abnormalities


9

Data Breakdown

40 Total Participants

23 Male17 Female

Age range: 23-79 yearsMean: 40

yearsSD: 17 years

30 subjects 55 direction

GE75%

40 subjects64 direction

Siemens100%

11 subjects 33 direction

GE28%


10

Analysis• Reproducible Objective

Quantification Scheme (ROQS) (Niogi, et al. 2007)

• 6 regions:1. Corpus Callosum (CC)2. Corticospinal Tract (CST) 3. Cingulum Bundle (CB)4. Superior Longitudinal Fasciculus

(SLF)5. Anterior Corona Radiata (ACR)6. Uncinate Faciculus (UF)

Introduction Methods Results Discussion References 11

Statistical Analysis

• Average fractional anisotropy scores • Wilcoxon-Mann-Whitney test

• Test statistical difference between groups

• Performed using SPSS Version 25.0• Local Variance


12

Cingulum Bundle


13

0.4

0.45

0.5

0.55

0.6

0.65

0.7

1 2 3 4 5 6 7 8

Frac

tiona

l Ani

sotr

topy

Cingulum Bundle

55 Direction 64 Direction 33 Direction

0

0.05

0.1

0.15

0.2

0.25

0.3

0 1 2 3 4 5 6 7 8

Loca

l Var

ianc

e

Cingulum Bundle - Local Variance


Corticospinal Tract

0.4

0.45

0.5

0.55

0.6

0.65

0.7

0.75

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Frac

tiona

l Ani

sotr

opy

Corticospinal Tract


0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

0 2 4 6 8 10 12 14 16 18

Loca

l Var

ianc

e

Corticospinal Tract - Local Variance



14

Superior Longitudinal Fasciculus


15

Anterior Corona Radiata

0.03

0.035

0.04

0.045

0.05

0.055

0 1 2 3 4 5 6 7

Loca

l Var

ianc

e

Anterior Corona Radiata – Local Variance



16

Uncinate Fasciculus

0.5

0.52

0.54

0.56

0.58

0.6

0.62

0.64

0.66

1 2 3 4 5 6 7 8

Frac

tiona

l Ani

sotr

opy

Uncinate Fasciculus


0

0.02

0.04

0.06

0.08

0.1

0.12

0.14

0.16

0.18

0.2

1 2 3 4 5 6 7 8

Loca

l Var

ianc

e

Uncinate Fasciculus - Local Variance



17

Corpus Callosum

0

0.1

0.2

0.3

0.4

0.5

0.6

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Loca

l Var

ianc

e

Corpus Callosum – Local Variance



18

Findings

Confirmed Findings• Systematic parameters impact

FA measurement• gradient directions, slice

thickness, voxel size, hardware

• Variations are not predictable and vary per tract

• Combining data = invalid• (Papadakis, et al. 1999) (Skare, et al. 2000) (Lebel,

et al. 2012)

Novel Findings• Homogeneity of the white

matter are scanner/system independent

• Alternate Approach• Combine data• Individual assessment

• Patent Submission in Progress


19

TBI patient, example• 27 year old professional

football player• Grade II concussion

(symptoms for more than 15 minutes without loss of consciousness

• Trace hemorrhage in the lateral ventricles on acute conventional MRI. No direct or indirect evidence of axonal injury on conventional MRI

• DTI local variance measure strongly suggests axonal injury involving the genu of the corpus callous, a frequently injured tract 0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Corpus Callosum VarianceAnterior to Posterior

Limitations

• Data Sets were Cross-sectional• Not every subject scanned on every scanner

• Local variance estimates were based on regions of interest• Future application of this technique will work as a continuous measure along

tractograms.


20

Future Research/Work

• Validate findings with optimized algorithm and data on multi-institutional datasets

• Patient testing:• Retrospective study on Professional Boxers• Prospective study on both controls and TBI patients

• Complete patent application• Seek Licensing to industry partners

• We already have potential buyers (Athlemetrics, LLC)


21

Acknowledgements

I would like to thank my my mentor, Science Research teachers, and parents for their continued support.

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Concussion is a subset of mild TBI. Generally, concussion is limited to the very mild end of mild TBI resulting specifically from an impact to the head. On the other hand, the severe end of mild TBI can manifest with loss of consciousness, severe symptoms, amnesia, dizziness, and headache. It also includes trauma from acceleration forces not associated with a direct impact.

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Novel Proof of Concept to Assess Multifocal Neuronal Disease in … · 2018. 6. 25. · White Matter Tracts • Altered by neurodegenerative disorders, medications, or neuropsychological