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August 17, 2019 Francesca Bagnato M.D.Ph.D Assistant Professor of Clinical Neurology TN Valley Health Care System Nashville Campus & Vanderbilt University Medical Center Imaging Spinal Cord Hidden Pathology Paralyzed Veterans of America Healthcare Summit 2019 Orlando FL

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Page 1: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

August 17, 2019

Francesca Bagnato M.D.Ph.DAssistant Professor of Clinical Neurology

TN Valley Health Care System Nashville Campus & Vanderbilt University Medical Center

Imaging Spinal Cord Hidden Pathology

Paralyzed Veterans of AmericaHealthcare Summit 2019

Orlando FL

Page 2: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

DISCLOSURESDr. Bagnato’s Research Lab is funded by the National MS Society (PP-1801-29686 and RG-1901-33190) and the National Institutes of Health (1R01-NS109114-01).

Dr. Bagnato acted a PI for Novartis Pharmaceuticals sponsored phase-IVstudy (Novartis VUMC64211).

Dr. Bagnato received honorary compensations for speaking bureau fromEMD Serono.

Page 3: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

LEARNING OBJECTIVESObjective #1: To summarize anatomy and mechanismsof spinal cord disease outside lesions;

Objective #2: To recognize the challenges associatedwith spinal cord imaging;

Objective #3: To describe how imaging can untanglenon-lesional “hidden” spinal cord pathology.

Page 4: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

SPINAL CORD ANATOMY (1)33 vertebral bones

https://scireproject.com/community/topic/spinal‐cord‐anatomy/

https://nba.uth.tmc.edu/neuroanatomy/L4/Lab04p01_index.html

Page 5: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

SPINAL CORD ANATOMY (2)

https://www.orthobullets.com/spine/2008/incomplete‐spinal‐cord‐injuries

Page 6: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

SPINAL CORD PATHOLOGY

The neuropathology of (various) diseases in the spinal cord may be dividedin two broad categories:

primary pathology spinal cord lesions

secondary pathology manifesting as retrograde and anterogradedegeneration of the axon and its cell body.

Page 7: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

SPINAL CORD PATHOLOGY

The neuropathology of (various) diseases in the spinal cord may be dividedin two broad categories:

primary pathology spinal cord lesions, and

secondary pathology manifesting as retrograde and anterogradedegeneration of the axon and its cell body.

Page 8: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

PRIMARY PATHOLOGY

Polio Multiple Sclerosis ALS

http://medicalhealthguides.blogspot.com

Page 9: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

ASA occlusion 3ry Syphilis Syringomyelia Vitamin B12 deficiency

http://medicalhealthguides.blogspot.com

PRIMARY PATHOLOGY

Page 10: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

From Freund et al. Lancet Neurology 2019

PRIMARY PATHOLOGY

Page 11: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Our virtues and our failings are inseparable, like force and matter. When they separate, man is no more…Nikole Tesla

Interstellar space 10^-10 Tesla 10^-6 Gauss

Earth's magnetic field 0.00005 Tesla 0.5 Gauss

Small bar magnet 0.01 Tesla 100 Gauss

Within a sunspot 0.15 Tesla 1500 Gauss

Big electromagnet 1.5 Tesla 15,000 Gauss

Strong lab magnet 10 Tesla 100,000 Gauss

Surface of neutron star 100,000,000 Tesla 10^12 Gauss

Magstar 100,000,000,000 Tesla 10^15 Gauss

1 Tesla = 65,000 magnetic field lines per square inch 7 Tesla = 70,000 times the earth’s magnetic field

Page 12: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

CHALLENGES IN SPINAL CORD IMAGING

1. SMALL

2. CLOSE TO MOVING ORGANS

3. CLOSE TO STRCTURES WIT DIFFERENT CONTRAST

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VISUALIZING LESIONS USING MRI

Conventional MRI plays a crucial role in the diagnostic workup of spinalcord pathology as it shows intrinsic lesions and extrinsic compression ofthe spinal cord.

Conventional MRI includes T2-weighted sequences, STIR (short-TIInversion Recovery) and T1-weighted sequences obtained after the injectionof the contrast agent Gadolinium.

Page 14: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Freund et al. Lancet neurology 2019

Modified rom Freund et al. Lancet Neurology 2019

Page 15: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Neurosarcoidosis: Radiological Manifestations (5) FIGURE 4.

NEUROSARCOIDOSIS

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MULTIPLE SCLEROSIS AND NMO

From Moccia et al. Ther. Adv Neurol. Disord. 2019

Page 17: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

STIR ARTIFACTS

http://mriquestions.com/gibbs‐artifact.html

Page 18: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

SPINAL CORD PATHOLOGY

The neuropathology of (various) diseases in the spinal cord may be dividedin two broad categories:

primary pathology spinal cord lesions, and

secondary pathology manifesting as retrograde and anterogradedegeneration of the axon and its cell body.

Page 19: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

From Freund et al. Lancet Neurology 2019

Spinal Cord Hidden Pathology

Degeneration

Distal to the injury (Wallerian)

Dying back or retrograde

Page 20: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

PRIMARY PATHOLOGY

Polio Multiple Sclerosis ALS

http://medicalhealthguides.blogspot.com

Page 21: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Imaging Spinal Cord Hidden Pathology

Page 22: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Spinal Cord Atrophy (1)Spinal cord atrophy is generally measured as the cross-sectional area atthe cervical level.

Moccia et al. Ther. Adv Neurol. Disord. 2019

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Spinal Cord Atrophy Measurements

Weeda et al. Neuroimage Clin 2019

axial slices starting from the most superior point of C1 and ending at a position 30 mm more inferior.

Page 24: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Winston Ann Neurol 2014

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Winston Ann Neurol 2014

Page 26: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

From Freund et al. Lancet Neurology 2019

Spinal Cord Hidden Pathology

Magnetization transfer imaging SWI Diffusion Tensor Imaging

Page 27: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

MTI is a quantitative technique that measures themagnetization exchange between freely mobileprotons and those associated withmacromolecules such as myelin or axonalmembranes MT ratio or MTR

Magnetization Transfer Imaging (MTI)

http://mriquestions.com/magnetization‐transfer1.html

Page 28: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Magnetization Transfer Imaging (MTI)

http://mriquestions.com/magnetization‐transfer1.html

MTR ~0.4

Page 29: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Magnetization Transfer Imaging (MTI)

http://mriquestions.com/magnetization‐transfer1.html

MTR ~0.4

MTR ~0.2

Page 30: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Magnetization Transfer Imaging (MTI)

From Martin et al. PLOS‐one 2018

Page 31: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

From Oh J et al. Neurology 2015

Page 32: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Diffusion Tensor Imaging (MTI)

https://mrgranato.wordpress.com/2018/09/28/osmosis-diffusion-homework-article-sept-28/

Page 33: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Diffusion Tensor Imaging (DTI)

http://mriquestions.com/magnetization‐transfer1.html

Page 34: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Diffusion Tensor Imaging (DTI)

http://mriquestions.com/magnetization‐transfer1.html

Radial diffusivity

Axial Diffusivity

Diagonal Diffusivity

(R+A+D)/3 Mean Diffusivity

Page 35: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Diffusion Tensor Imaging (DTI)

http://mriquestions.com/magnetization‐transfer1.html

Page 36: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Diffusion Tensor Imaging (DTI)

http://mriquestions.com/magnetization‐transfer1.html

Water if more free to move in diseased tissue!

Page 37: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Diffusion Tensor Imaging (DTI)

From Oh J et al. Neurology 2013

Page 38: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

DTI in Radiologically Isolated Syndrome

From Oh J et al. Neurology 2013

Page 39: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

DTI in ALS

From Valsasina J et al. JNNP 2007

Page 40: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

DTI in ALS

From Valsasina J et al. JNNP 2007

Page 41: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

DTI in Experimental Trauma

From Wang‐Leandro J Trans Med 2018

Page 42: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

SUMMARY#1: Both focal as well as diffuse and hidden spinal corddisease may affect patients with both traumatic andneurodegenerative conditions.

Objective #2: Spinal cord MRI is feasible, advancing butchallenging due to distinct anatomical features of thespinal cord.

Objective #3: Advanced quantitative MRI techniques canuncover otherwise hidden spinal cord pathology and candeliver biomarkers of neurodegeneration to be used asproof of concept clinical trials on neuroprotection andrepair.

Page 43: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

Thank You for your kind attention

Page 44: Imaging Spinal Cord Hidden Pathology2019.summitpva.org/sites/2019.summitpva.org/files/pdf/talks/P1955… · Nikole Tesla Interstellar space 10^-10 Tesla 10^-6 Gauss Earth's magnetic

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