MRI and fMRI: History, Components, and Signal Measurement

A Brief History of MRI & fMRI

• 1921/22 – Quantum Spin Discovered (Stern & Gerlach): Showed that atomic particles have intrinsic quantum properties (spin), a foundation for magnetic resonance.
• 1946 – Nuclear Magnetic Resonance (NMR) in Bulk Matter (Bloch & Purcell): Demonstrated that nuclei in a magnetic field absorb and re-emit radio waves, leading to MRI development.
• 1971 – First Medical Application of MRI (Damadian): Showed cancerous tissue has different NMR signals than healthy tissue.
• 1973 – First MRI Image (Lauterbur): Introduced spatial gradients, allowing MRI to form an image.
• 1990 – BOLD Contrast in fMRI Discovered (Ogawa): Blood oxygenation levels influence MRI signal due to deoxyhemoglobin’s paramagnetic properties; Laid the groundwork for functional MRI (fMRI) to track brain activity.

MRI Components & Safety

MRI Components:

• Superconducting Magnet: Generates strong, static magnetic field (B0).
• Gradient Coils: Modify B0 spatially to enable imaging.
• RF Coils: Transmit & receive radio waves for excitation & signal detection.
• Shim Coils: Correct inhomogeneities in B0.

MRI Safety Risks:

• Ferromagnetic Objects: Can become projectiles in strong magnetic fields.
• RF Heating: Can cause burns if proper precautions aren’t taken.
• Acoustic Noise: Can reach 130 dB (hearing protection is required).

Key MRI Concepts

• Larmor Frequency: The rate at which protons precess in B0. Higher B0 → Faster precession.
• Magnetic Susceptibility:
  • Diamagnetic: (weakly repelled by B0): Oxygenated hemoglobin, water.
  • Paramagnetic: (attracted to B0): Deoxygenated hemoglobin (dHb).
  • Ferromagnetic: (strongly attracted): Iron, cobalt, nickel (dangerous in MRI).

MR Signal Measurement & Relaxation

• Free Induction Decay (FID): Signal loss due to spin dephasing.
• T1 Relaxation (Longitudinal Recovery): Time for spins to realign with B0.
• T2 Relaxation (Transverse Decay): Time for spins to lose phase coherence.
• T2*: Faster signal decay due to inhomogeneities in B0 (exploited in fMRI). 1/T2* = 1/T2 + 1/T1

MRI Image Formation & Spatial Encoding

• Slice Selection (Gz Gradient + RF Pulse):
  • RF pulse excites protons only at a specific frequency (slice plane).
  • A negative Gz gradient corrects phase dispersion for uniform signal.
• Frequency Encoding (Gx Gradient): Spins at different x-locations precess at different frequencies.
• Phase Encoding (Gy Gradient): Spins at different y-locations accumulate different phase shifts.
• Final Image Reconstruction: Uses the Fourier Transform to convert k-space data into an MRI image.

K-Space & MRI Contrasts

• K-space is the raw data storage for MRI scans.
  • Center of k-space → Contrast (low spatial frequencies).
  • Outer regions of k-space → Sharpness (high spatial frequencies).
• MRI Contrast Mechanisms:
  • T1-weighted: (Short TR, Short TE) → Highlights fat, gray matter.
  • T2-weighted: (Long TR, Long TE) → Highlights fluids (CSF, edema).
  • Proton Density (PD-weighted): Reflects tissue composition.

Functional Hyperemia (FH)

• Functional Hyperemia (FH): Increase in local blood flow due to neural activity (sensory, motor, or cognitive event).
• Brain consumes ~20% of body’s energy but has no energy stores → FH ensures oxygen & glucose delivery.
• FH is Feedforward Contrary to Roy and Sherrington’s hypothesis Blood flow increases before metabolic demand is met. Ngai (1988) show CBF response to sciatic nerve stimulation in a rat, confirming Roy/ Sherrington’s indirect observation with cerebral expansion/contraction
• Key Study (Leithner et al., 2010): Blocking FH did not change neural activity, proving FH’s supportive role rather than a controlling one
• To dissipate heat, as in the peripheral organs of the body
• To remove waste and toxins
• To meet metabolic demand by delivering necessary nutrients to do work. no definitive answers as to what physiological role is served by FH; best guess: over compensatory delivery of O2 caused by the increase in CBF is to ensure that O2 levels in the tissue remain high enough to meet the metabolic demands of neuronal cellular components that are distant from nearby capillaries
• We are “…watering the entire garden for one thirsty flower” (Malonek & Grinvad, 1996)
• Whatever its function, fMRI would likely not exist, at least in its present form without FH.

BOLD Signal & fMRI

• BOLD (Blood Oxygenation Level Dependent) Signal:
  • Neural activity → increased blood flow (rCBF) → More oxygenated blood → Reduced dHb → Stronger MRI signal.
  • BOLD is an indirect measure of neural activity (tracks blood flow, not neurons directly).
  • Over compensatory delivery of O2 caused by the increase in CBF is to ensure that O2 levels in the tissue remain high enough to meet the metabolic demands of neuronal cellular components that are distant from nearby capillaries
  • We are “…watering the entire garden for one thirsty flower” (Malonek & Grinvad, 1996)
  • Whatever its function, fMRI would likely not exist, at least in its present form without FH.
  • dHb: no oxygen, paramagnetic (attracted to magnetic field), causes magnetic field distortions
• Gradient Echo (GRE) is used for fMRI:
  • Preserves T2 weighting* (spin-echo cancels BOLD contrast).
  • Allows rapid imaging (EPI – Echo Planar Imaging).
  • Gradient-Echo (GE) fMRI → Strong BOLD contrast (T₂ effects visible).
  • Spin-Echo (SE) fMRI → Cancels most BOLD contrast (corrects for T₂ dephasing, good for T2 but we want T2*).
  • less effective for detecting neural activity in fMRI.

The BOLD Response: Temporal Dynamics

• Initial Dip (0-2 sec): Small dHb increase due to oxygen use.
• Peak Response (~5 sec): Overcompensation of blood flow reduces dHb, increasing signal.
• Post-Stimulus Undershoot (10-30 sec): Oxygen use remains high while blood flow decreases.
• Balloon Model: Venules expand like a balloon, creating a delay in the return to baseline.

Linearity of the BOLD Signal

• For stimuli spaced >2 sec apart → BOLD responses sum linearly.
• For stimuli <2 sec apart → Nonlinear effects occur (accentuated 2nd response).
• Key finding: BOLD reflects synaptic input more than action potentials (LFPs > Spiking Activity).

Key MRI & fMRI Terms

• Larmor Frequency: Determines precession rate of protons in a magnetic field. Higher B0 –> higher Larmor; Determines RF pulse frequency for excitation & contrast.
• Free Induction Decay (FID): Loss of MRI signal due to proton dephasing after RF pulse excitation. Causes rapid signal decay.; Rapid signal loss unless refocused by spin echo or GRE
• T1 Relaxation (Longitudinal Recovery): Protons realign with B0 over time, restoring longitudinal magnetization. Controls T1-weighted contrast.; Shorter T1 → Brighter signal (e.g., fat), Longer T1 → Darker (e.g., CSF).
• T2 Relaxation (Transverse Decay): Protons lose phase coherence due to interactions with each other. Controls T2- weighted contrast.; Shorter T2 → Darker signal (e.g., muscle), Longer T2 → Brighter (e.g., CSF).
• T2* Relaxation: Faster decay due to both T2 effects and magnetic field inhomogeneities. Basis for BOLD contrast in fMRI.; T2* causes faster signal decay, exploited in fMRI BOLD imaging.
• Gradient Coils & Spatial Encoding: Gz, Gx, and Gy gradients modify B0 field strength in specific directions to encode spatial location.; Spatial localization of MRI signal, enabling image formation.
• Slice Selection (Gz Gradient): RF pulse + Gz gradient excites only a selected slice of tissue. Negative Gz gradient rephases spins.; Allows targeting of specific anatomical regions for imaging.
• Frequency Encoding (Gx Gradient): Gx gradient makes protons at different x-positions precess at different frequencies. Used for frequency encoding.; Encodes spatial information along the x-axis for image reconstruction.
• Phase Encoding (Gy Gradient): Gy gradient induces phase shifts in protons along the y-axis. Used for phase encoding.; Encodes spatial information along the y-axis for image reconstruction.
• K-Space & Image Reconstruction: Raw data is stored in k-space, which is transformed via Fourier Transform to produce the final MRI image; Determines resolution & contrast; center encodes contrast, periphery encodes details.
• Repetition Time (TR): Time between successive RF excitation pulses. Determines how often the sample is excited.; Short TR = More T₁ contrast, Long TR = Less T₁ effect (useful for T₂-weighting).
• Echo Time (TE): Time between RF pulse and signal acquisition. Determines how soon we record the signal.; Short TE = Less T₂ contrast, Long TE = More T₂ contrast (fluid appears bright).