diffusion physics - thermal agitation - in steady state, the motion of water is dominated by thermal...
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Diffusion Physics - Thermal Agitation
- In steady state, the motion of water is dominated by thermal agitation.
-This causes “random” motion of water within a compartment.
Diffusion Physics - Thermal Agitation
-The “rate” of water motion is determine by a diffusion coefficient, “D”.
-Mean displacement of water molecules is related to “D” by Einstein’s equation:
Detecting Diffusion with MRI - Intravoxel Incoherent Motion
From Ellingson, Concepts in MR, 2008
Detecting Diffusion with MRI - Intravoxel Incoherent Motion
Detected DWI Signal
MRI Signal w/o Diffusion Sensitivity
Phase of “Tagged” H2O Function of Diffusion Gradients
Diffusion Coefficient
Factors that affect diffusion coefficient, D
-Diffusion Time, t -Physical time between gradients used to “tag” H2O
-Size of Compartment(s)- If we set a limit for r, then we observe an apparent diffusion coefficient, ADC
-Tortuosity of the Compartments- More tortuous paths look like slow diffusion
-Temperature
-Viscosity
*** We can only measure “ADC” because of all the factors that change “D”! ***
Diffusion Tensor Imaging (DTI)• Diffusion anisotropy can occur when compartments are not symmetric
• Diffusion may be higher in different directions
• To determine diffusion anisotropy, we use Diffusion Tensor Imaging (DTI)
• DTI uses diffusion sensitizing gradients to determine ADC in different directions
• From these measurements we construct the mathematical tensor
• In this way, DTI more accurately models the geometry of tissues
Isotropic Diffusion Anisotropic Diffusion
Diffusion Tensor Imaging (DTI)The Diffusion Tensor:
Isotropic Diffusion
1 = 2 = 3
Anisotropic Diffusion
1 > 2, 3
From Ellingson, Concepts in MR, 2008
Davidoff, A., Handbook of the Spinal Cord
• MR constraints largely limit ADC measurement to the extracellular compartment.
• Diffusion in the spinal cord is highly anisotropic for both gray matter and white matter
Diffusion MR Characteristics of theCentral Nervous System
From A.Todd, Univ. GlascowFrom Ellingson, Concepts in MR, 2008
• Transverse ADC (tADC) is dependent on (Schwartz, 2005)
Axon Counts = tADC Extracellular Volume = tADC Myelin Volume = tADC
• Longitudinal ADC (lADC) is dependent on (Song, 2003; 2002; Sun, 2006; Ellingson, 2008)
– Structural and Functional Integrity of Axons
– Microfilament & Neurofilament Density
– Axonal Transport System Integrity
Diffusion MR Characteristics of theCentral Nervous System
From Ellingson, Concepts in MR, 2008
DTI Tractography
• In the CNS, lADC > tADC & 1 is parallel to axon orientation
• ADC is consistent across pulse sequences (Ellingson, AJNR, 2008)
Ellingson, 2008
Diffusion MR Characteristics of theCentral Nervous System
• Anisotropy is preserved across surrogates (Ellingson, Concepts in MR, 2008)
Diffusion MR Characteristics of theCentral Nervous System
• ADC changes across the length of the spinal cord (Ellingson, AJNR, 2008; Ellingson, JMRI, 2008)
Human
Rat
Rostral Caudal
Pathology & DTI in Spinal Trauma
Pathology of Acute SCI• Mechanical Injury:
– Stretching and tearing of axons immediate death of all damaged cells.
• Hypoxia and Ischemia:
– Blood flow to injury is restricted.
– Anaerobic metabolic processes in viable tissue, other tissues become necrotic.
• Hemorrhage & Vasogenic Edema:
– In contusion injury, hemorrhages start in central gray matter and spread radially.
– Early vasogenic edema forms due to blood constituents leaving vasculature.
• Damage to Axon Transport Systems:
– Microtubules and neurofilaments begin to degrade.
Normal Mechanical Injury
Vasogenic Edema
From Ellingson, Concepts in MR, 2008
DTI in Acute SCI• Mechanical Injury:
– Overall ADC at lesion site due to lack of boundaries to diffusion
• Hypoxia and Ischemia:
– Cause ADC
• Hemorrhage & Edema:
– Causes ADC at lesion site due to lack of boundaries to diffusion
• Damage to Axon Transport Systems:
– Causes lADC
Rat - Ex Vivo
(Ellingson, JMRI, 2008b)
lADCtADC
From Ellingson, Concepts in MR, 2008
Pathology of Subacute SCI• Reactive Cells:
– Active microglia increase in density
– Active Astrocytes hypertropy and line the cavity wall
• Anterograde and Retrograde Degeneration:
– Axons form retraction bulbs at proximal ends
– Demyelination occurs
– Proximal axons begin to swell
– Distal axons are dissolved
• Gray Matter Morphological Changes:
– Damaged axon nuclei move to eccentric locations within the cell body.
– Neurons begin to hypotrophy and dendrites retract
• Cytotoxic Edema– Axons and soma swell, the
extracellular space decreases
Normal Reactive Cells
Cytotoxic Edema
From Ellingson, Concepts in MR, 2008
DTI in Subacute SCI• Reactive Cells:
– Glial scar changes 1 orientation
(Schwartz, 2005)
– High density microglia ADC
– Tortuosity from activated astrocytes causes ADC
• Anterograde and Retrograde Degeneration:
– tADC during demyelination
– lADC due to axon transport damage
– ADC due to axon swelling
• Gray Matter Morphological Changes:
• Vasogenic Edema
– Axons and soma swell, the extracellular space decreases
– This causes ADC
Rat - Ex Vivo
(Ellingson, JMRI, 2008b)
lADCtADC
From Ellingson, Concepts in MR, 2008
Pathology of Chronic SCI• Long-term Axon Degeneration
– Progressive demyelination
– Loss of large diameter axons
– Widespread spreading of cysts
– Retrograde & Transneuronal degeneration damages whole spinal tracts
• Gray Matter Morphology Changes
– Chromatolysis
– Nuclear Changes
• Spinal Cord Atrophy
Normal Atrophy
+ Axon Loss
Normal MNs Chronic SCI MNsFrom Ellingson, Concepts in MR, 2008
DTI in Chronic SCI
Cavity Formation
Remote Changes
Rat - Ex Vivo
(Ellingson, JMRI, 2008b)
DTI in Chronic SCIRat - Ex Vivo
(Ellingson, JMRI, 2008b)
DTI in Chronic SCIChronic Human SCI
(Ellingson, AJNR, 2008b)
C5 Complete Injury
Rostral-Caudal Asymmetry at Lesion Epicenter
Functional Correlates of DTI
Axonal Damage (Song, 2003; 2002; Nair, 2005; Sun, 2006)
↓ Longitudinal ADC (lADC)
Myelin Damage (Song, 2003; 2002; Nair, 2005; Sun, 2006)
↑ Transverse ADC (tADC)
Functional Correlates of DTI
Normal SCI
No temporalCoherence
Loss ofAmplitude
Functional Correlates of DTI
C-fiber input to LSTT
(Valeriani, 2007; Li, 1991; Latash, 1988)
A-fiber input to MSTT
(Valeriani, 2007; Latash, 1988)
Ellingson, J Neurotrauma, 2008, In Press
Functional Correlates of DTIFrom Ellingson, Biomed Sci Instrum, 2008 & Congress Neurological Surgeons, 2008
Conclusions
• DTI is highly sensitive to the structural integrity of the spinal cord.
• DTI can be used to monitor the progression of SCI from acute through chronic stages
• DTI may also be sensitive to the functional integrity of the spinal cord.
• Future studies will be aimed at determining if DTI can predict long-term functional recovery in incomplete SCI
Thank You• Brian Schmit, Ph.D., Dept. of Biomedical Eng., Marquette University• Shekar Kurpad, M.D., Ph.D., Dept. of Neurosurgery, MCW• John Ulmer, M.D., Dept. of Radiology, MCW• Maria Crowe, Ph.D., Dept. of Neurosurgery, MCW• Kathleen Schmainda, Ph.D., Dept. Radiology & Biophysics, MCW• Kristina Ropella, Ph.D., Dept. Biomed. Eng., Marquette University
• Funding: – NIH R21, Brian Schmit (PI)– Falk Foundation– Marquette University– VA Medical Center, Milwaukee, WI– Bryon Riesch Paralysis Foundation