Functional Imaging Techniques Perfusion Diffusion fMRI Spectroscopy Real-Time Cardiac Motion / Perfusion Microscopy
Feb 24, 2016
Functional Imaging Techniques
PerfusionDiffusionfMRISpectroscopyReal-Time Cardiac Motion / PerfusionMicroscopy
Perfusion & Diffusion
Perfusion of tissues via capillary bed permits delivery of O2 & nutrients to cells & removal of waste products.
Diffusion relates to random motion of H2O molecules in tissues. Interaction w/ local cellular structures produces anisotropic, directionally-dependent diffusion.
Perfusion Weighted Imaging
Measure of quality of vascular supply to tissue Regional blood volume & flow Mean transit time
Tissue Activity Since vascular supply usually related to metabolism
Tagging water in arterial blood during acquisition Endogenous: Spin labeling
Saturated blood just upstream of ROI serves as tracer EPI used Weak SNR
Exogenous: Gd contrast Exploits magnetic susceptibility of Gd T2 or T2* weighting EPI Quality of injection & timing of acquisition critical
Spin Labeling
Solid lines: imaging slice Dashed line: tagging plane where H2O protons in inflowing arterial blood are magnetically tagged by RF inversion pulse.
Quantitative estimates of cerebral blood flow can be obtained by measuring signal changes between tagged images & baseline untagged images.
Unenhanced sagittal T1-W MRI shows continuous inversion arterial spin-tagging technique.
Result
Images show quantitative cerebral blood flow maps.
Displayed are five of 10 slice locations extending from level of mid lateral ventricle to level of supraventricular white matter.
Artifacts from high flow in superior sagittal sinus are noted anteriorly and, to lesser extent, posteriorly.
Total imaging time was approximately 5 min
Multiple slices of brain obtained using multi-slice arterial spin-tagging MR perfusion imaging technique.
Gd ContrastNon-Contrast CTT
T2W MR
Negative finding for cortical infarction
Increased signal right calcarine cortex
DWI MR
Larger area of signal abnormality, consistent w/ infarction
CBV Map
MTT Map
Larger area of perfusion deficit; infarction core w/ surrounding tissue at risk
↑ transit time, corresponding to infarction core w/ surrounding tissue @ risk
43 yo man w/ acute onset left-sided weakness & visual changes; found to have left homonmous hemianopsia
↑CBV↓CBV
↑MTT
Perfusion Images
Pre-injection
Post-injection
Time Intensity Curve
EPI Time Series
Time Signal Curve
Tissue Concentration-Time Curve Area
Cerebral Blood Volume
Cerebral Blood Flow
Mean Transit Time
Height
Area/Height
Tissue Response Function
Arterial Input Function
Deconvolve
Perfusion Uses
Evaluate ischemia disease Areas of ↓perfusion on CBV map stroke
Malignancy of neoplasms ↑Tissue metabolism/perfusion ↑Perfusion on CBV map
Characteristic patterns seen in Hepatocellular carcinoma Metastases Hemangiomas
Evaluation of tissue viability & metabolism of vascular organs Heart Visceral structures Brain
Renal Artery Stenosis
Restricted vs. Free Diffusion
Restricted DiffusionHigh cellularity. Reduced extracellular space & cell membranes act as barrier to water movement
Free DiffusionLow cellularity (relative ↑ in space) & defective cell membrane (movement allowed between extra/intra cellular spaces) allows freer water movement
Water molecules
w/in extracellular space
w/in intracellular space
w/in intravascular space
2 Types of DW images
Diffusion/Trace images Normal
More H2O mobility ↑ signal loss Injury
↓ water mobility Brighter than normal tissues
Apparent Diffusion Coefficient (ADC) Maps Requires ≥ 2 acquisitions w/ different DWI parameters Post processing calculates ADC for each voxel Low ADC
High signal intensity on calculated image Restricted diffusion
DWI Pulse Sequence
90° 180°T2-weighted SE
RF
Signal
SignalStatic molecules
Moving water molecules
Diffusion-sensitizing gradients
Strong gradients applied symmetrically about refocusing pulse Signal difference based on mobility & directionality of H2O diffusion
Ischemia
Acute ischemic stroke lesion In early stroke, soon after ischemia onset but before infarct, cells swell & absorb water from extra-cellular space.
Since cells full of large molecules & membranesdiffusion restricted↓ADC
DWIDiffusion Coefficient Map
Sensitive indicator for early detection of ischemic injuryDrastic ↓ of ADC compared to unimpaired tissueCan show irreversible & reversible Ischemic lesionsPotential for discriminating salvageable tissue from irreversible damage
Directional Effects Diffusion gradient can be applied along all 3 axes All together, or Individually
Sensitize sequence to restricted diffusion along a particular axis
Example: White Matter tracts take specific courses through brain &
spinal cord Anisotropic tissue
May enable imaging of certain WM diseases Diffusion Tensor Imaging
In this image, the axons are colored according to orientation. Fibers running between the front and back are blue, those between right and left are red, and those running between the brain's interior and exterior are green.
DWI Uses Currently:
Brain after infarction Differentiate:
Malignant from benign lesions Tumor from edema & infarction
Neonatal brains Difficult to distinguish infarction & myelinating brain Map out myelination patterns in pre-term infants
Additional areas being explored: Characterizing
Liver lesions Breast & prostate tumors
Differentiating between Mucin-producing pancreatic tumors & other tumors Pathological & traumatic fractures
Imaging Skeletal muscle injury Left ventricular damage after myocardial infarction
Assessing bone bruising Overlaying DWI onto T1W images
combine structural & functional data
Diffusion-Perfusion Mismatch
Blood VolumeLesion has reduced CBV
Blood VolumeLarge perfusion deficit
Blood VolumeReduced flow around lesion
T2-wtEarly stroke not seen
Diffusion-wtClear depiction of lesion
Apparent DiffusionAcute stroke has low ADC
DWI PWI
fMRI
Mechanism Exploit differences in magnetic susceptibility
between oxyhemoglobin & deoxyhemoglobin
Oxyhemoglobin Oxygen bound to hemoglobin Magnetic properties of Fe largely suppressed Diamagnetic
DeoxyHb Paramagnetic ↑ T2* decay Endogenous contrast agent
Cerebral Metabolism
@ rest Venous blood contains equal parts oxy- & deoxyhemoglobin
During Exercise Metabolism↑ ↑O2 needed Concentration of oxyhemoglobin↓
Brain Very sensitive to ↓ concentrations of oxyhemoglobin ↑Blood flow to local vasculature accompanies neural activity
Local ↓ in deoxyhemoglobin Because ↑ blood flow occurs without ↑ in O2 extraction
BOLD Blood Oxygenation Level Dependent acquisition
Multiple images acquired before stimulus during repeated stimulus
Post-stimulus data sets Pre-stimulus data sets Metabolic activity resulting from repeated task-induced stimulus Repetitions to ↑ SNR
If resulting signal > correlation threshold, color overlay placed on gray scale anatomic image
Pulse Sequences High speed & T2*-weighting required EPI
As little as 50 ms for 64 x 64 matrix GRE
↑ Spatial resolution Much longer exam time Cooperative subjects
Applications Research
Neuropsychological studies Cognitive studies
Clinical practice Localizing functional regions of motricity / language for
pre-operational purposes before neurosurgical excision Determine hemispheric dominance of language
(calculate laterality index) Assess possibilities of functional recuperation
Evaluation of stroke, pain, epilepsy, behavioral problems Predict tubular necrosis in kidneys & Mesenteric ischemia
Alternating R/L finger tappingBlack curve show correlated BOLD signals (Right)Red indicates right finger tap, Blue left.
fMRI
MR Spectroscopy
MRS of Brain
Description
In vivo exploration of molecular composition of tissue
Identifies metabolites in physiological /pathological processes Proton ()
Most commonly used Highest SNR 10-15 min added onto conventional scan
Sodium () Phosphorus ()
Mechanism
Metabolite frequencies differ slightly Slightly different resonance frequencies due to
electron cloud shielding Frequency shift α magnet strength
Exploiting chemical shift to determine relative quantity of chemical
Relative metabolite concentrations plotted Relative intensities vs. frequency shift Area under peaks = quantity of metabolite
Example Spectrum
Spectrum obtained in healthy liver shows frequency locations of H2O & lipid peaks.
By convention, x-axis plotted as downward shift relative to H2O frequency.
frequency (ppm)
Frequency Shift Differs for each magnetic field intensity
@1.5 T metabolite frequencies range from 63 – 64 MHz
Scale changed to ppm Allows comparison for different magnet strengths Reduces large unwieldy numbers to more manageable size
Calculated by: [Metabolite frequency Reference frequency] Operating frequency
of MR Reference often water
4.26 ppm
Advantages of higher field strengths (3.0 vs. 1.5 T) Better separation of peaks Higher SNR
Water/Fat Suppression
Conventional MRI Total signal from all protons used
MRS need to suppress fat & water These peaks are huge compared to other metabolites
1̴0,000x higher Other peaks invisible on same scale
Suppression techniques CHESS (chemical shift) STIR (inversion recovery) Often area evaluated is away from fat structures
only water needs to be suppressed
Brain MRS Metabolites
Abbreviation
Metabolite Shift (ppm) Properties
Cho Phosphocholine
3.22 Membrane turnover, cell proliferation
Cr Creatine 3.02 & 3.93 Temporary store for energy-rich phosphates
NAA N-acetyl-L-aspartate
2.01 Presence of intact glioneural structures
Lactate 1.33 (inverted)
Anaerobic glycolysis
Lipids Free fatty acids 1.2-1.4 Necrosis
Metabolite Peak Ratios
Ratio Normal AbnormalNAA/CR 2.0 <1.6NAA/Cho 1.6 <1.2Cho/Cr 1.2 >1.5
Tumor metabolites:
↑Cell turnover causes ↑Cho concentration
Corresponding ↓of NAA peak caused by loss of healthy glioneural structures
Cr peak may also ↓, depending on energy status of tumor
Lipid peak sign of hypoxia-likelihood of high-grade malignancy
Single Voxel MRS
Single voxel sampling area Volume ~1 cm³
STEAM Stimulated Echo Acquisition Mode
90° excitation pulse, 90° refocusing pulse W/ gradients to define each voxel dimension
↓ TE & superior voxel boundaries ↓ SNR
PRESS Point Resolved Spectroscopy
90° excitation pulse, 180° refocusing pulse in each direction
FT voxel data Separates composite signal into individual frequencies
MRS Uses Serially monitor biochemical changes in
Tumors Stroke Epilepsy Metabolic disorders Infections Neurodegenerative diseases
Plan therapy
Biopsy guidance
Aid in prognosis
Spectra from • normal brain tissue • brain metastases • necrosis • gliomas of different grades
Examples
Normal brain Melanoma metastasis
Lung metastasis Lung metastasis
Grade 2 glioma Grade 2 glioma Grade 3 glioma Grade 3 glioma
Grade 4 glioma Grade 4 glioma Grade 4 glioma Center of grade 4 glioma
Prostate Imaging
GliomaGrade 2 Grade 3 Grade 4
Spectra w/ metabolic abnormalities shadedthose w/ peaks corresponding to lactate or lipid marked with “∗”
Multiple Sclerosis
Multi-voxel MRS
Multiple voxels defined using CSI Volume ~1cm³ 1, 2, or 3 planes overs rectangular block of several cm
MRSI Magnetic Resonance Spectroscopic Imaging Signal intensity of 1 metabolite color coded for each voxel
According to concentration Generated parameter maps superimposed on anatomic MRI
SVS performed 1st to make initial diagnosis SNR high All metabolites represented
Post contrast T1-weighted
Relative CBV
Non-enhancing right frontal mass
Elevated rTBV compared w/ contralateral normal tissue
decrease
increase
NAA/Cr ratio Cho/Cr ratio
Right Frontal Anaplastic Oligoastrocytoma
MR Microscopy
Comparison of MR microscopy & conventional pathology sections
Uses
Pathology applications Study models of disease, toxicology, effects of drug
therapies SNR↓ as voxel size↓
Very high field required Dedicated ultra-small coils
Clinical Bone & joint imaging
Esp. hyaline cartilage
In vivo μMR
in vivo MR microscopic image of human forearm skin acquired using a 1.5 T whole body imagerDepth resolution: 38 µm, measurement time: 7 min
Patellar cartilage
Interventional MRI
Advantages Intra-operative acquisition of MR images w/out moving
patients Image-guided stereotaxy w/out pre-op imaging Real-time tracking of instruments Precise location area under examination Continual monitoring of procedure in 3D
Challenges Expensive Surgical instruments
Non-ferromagnetic Produce minimum susceptibility artifacts
Anesthetic & monitoring equipment must be MR safe
Equipment
Uses Liver imaging & tumor ablation
Using laser therapy Ablation via heat
Using cryotherapy Ablation via extreme cold
MRI only technique that can discriminate different tissue temperatures T1 & T2 temperature dependent
Interstitial Laser Therapy (ILT) Laser energy delivered percutaneously to various depths in tissue EPI used for real-time intraoperative assessment of heat
distribution
Breast imaging & benign lump excision Orthopedic & kinematic studies Congenital hip dislocation manipulation & correction Biopsies Functional endoscopic sinus surgery
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