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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