perfusion imaging - 1und1.de

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Perfusion Imaging

Matthias Günther1,2,3

1 Fraunhofer MEVIS, Institute for Medical Image Computing 2 Faculty 01 (Physics/Electrical Engineering), University Bremen

3 mediri GmbH, Heidelberg, Germany

Overview

Blood flow and perfusiondefinition

Quantification of perfusiontracer-kinetics: steady-state, bolus-tracking

Basics of spatial perfusion measurement techniques

Pros and cons of imaging techniques

Blood flow and perfusion

Perfusion means transport of blood to unit volume of

tissue per unit time

Supplies cells with oxygen and other nutrients

Important parameter for status and activity of tissue

A lot of effort was put into measurement

What is perfusion?

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Background: why measure perfusion?

• All organs are critically dependent on blood supply for homeostasis

• Default in blood supply results in ischemia, or the lack of oxygenation to the organ

• This in turn leads to energy failure, cytotoxic edema, and cell death

Blood flow and perfusion

Macro-vascular: blood flow

volume per time

unit: [ml/min]

Micro-vascular: perfusion

latin: perfusio = to moisten

volume per time per tissue

unit: [ml/min/g]

Perfusion is often incorrectly called blood flow

Perfusion ≠≠≠≠ blood velocity ≠≠≠≠ blood volume!

What is the difference between blood flow and perfusion?

What is perfusion?

Circulation

Perfusion

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Measurement of perfusion

Basic idea of perfusion measurement

1. Use of tracer, either through breathing or intravenous injection

2. Tracer is transported to tissue of interest due to blood flow

3. Local tracer concentration is measure of perfusion

where: Ct=Cumulative tissue clearance Ca=Influx concentration

Ce=Efflux concentration P=Perfusion

Based on Ficks Law:


Two groups of measurement technique:

• Steady-State (equilibrium)

historically older technique, mostly attributed to technical

limitations

• Bolus-tracking (non-equilibrium)

more advanced, more complex modeling possible

Basic idea of perfusion measurement


Steady-State technique

Trying to reach constant level of tracer in body.

Continuous infusion instead of singular bolus (breathing of gas)

No modeling necessary to estimate relative perfusion, more

quantitative analysis using Kety-Schmidt-model

Limited possibility to generate additional parameter maps

Useful for ”slow” imaging modalities

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Kety-Schmidt model

Kety and Schmidt, Am J Physiology, 1945, 53-66. Kety and Schmidt, J Clin Invest, 1948, 27:476-483.

Historically used to model uptake of nitrous oxide (N2O, “laughing gas”)

Measurement of arterial and venous

concentration

Steady-state:

Ct(t) constant

Ct proportional to volume of tissue


ρ Partition coefficient for water: proportionality constant for tracer concentration in tissue

and blood

λ decay constant: depending on tracer, can be radioactive (e.g. PET: decay of 15O, ASL: T1-

relaxation of labeled magnetization, DCE: physiological half-life)

Arterial inflow Venous outflow decay

Equilibrium assumption:

Steady-State techniqueModification:

Imaging techniques allow measurement of Ct

Ce is not measured

but at equlibrium:


Arterial inflow Venous outflow decay

Calculate perfusion:

Needed is: tracer concentration Ca and Ct,

ρ partition coefficient for water,

λ decay constant


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Bolus-tracking technique

Also known as dynamic imaging approach or first-pass technique.

Method:

• Injection of tracer as fast as possible

• Observe passage of tracer bolus (venous outflow, tissue concentration)

• tracer kinetics for non-diffusable tracers (Zierler-Meyer-model)

• non-equilibrium

• time-dependent tracer concentration

Zierler KL. Fed Proc. 1965 Sep-Oct;24(5):1085-91.



Method of evaluation depends on injection speed (length of bolus)Tofts PS,Berkowitz BA. "Measurement of capillary permeability from the Gd enhancement curve: a comparison

of bolus and constant infusion injection methods." Magn Reson Imaging. 1994;12(1):81-91



Venous outflowArterial inflow

tissue

Various models, e.g.:

Single-compartment model

Two-compartment model

Three-compartment model

„tissue“-compartment

microvasculature

tissue

micro-

vasculature

extra-cellular

compartment

intra-cellular

compartment

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Tracer-bolus Convolution with

Response-function tracer-concentration

in tissue

ctissue

time t

Ctissue

ctissuecart

= blood volume

amplitude ~ perfusion

model-free

after deconvolution

width = mean transit time (MTT)

Central volume theorem:

MTT=blood volume / perfusion

after deconvolution

Time to peak (TTP) after deconvolution

slope after deconvolution

Cart

What is perfusion? Parameters …

• The Cerebral Blood Flow (CBF, Ft, f ) can be defined as the steady state

delivery rate of blood to the tissue capillary bed. It is measured in

ml/min/100g

• The Cerebral Blood Volume (CBV) is the amount of blood in the tissue. It is

measured in ml/100g

– In physiology, the regional CBV (rCBV) is defined as the amount of blood in the

capillaries

• The Mean Transit Time (MTT) can be defined as: MTT = CBV / CBF. It is

measured in s.

• The Bolus Arrival Time (BAT) or Arterial Transit Time is the time taken by a

bolus of indicator to reach the tissue, measured in s.

Perfusion imaging approaches

Image-based perfusion estimation:

Necessary:

• tissue concentration of tracer Ct

• arterial concentration of tracer Ca

Difference steady-state and bolus tracking:

steady-state: in principle, only one measurement necessary (at equilibrium)

in practice, slow sampling, since equilibrium is not reached

bolus tracking: time-dependent Ct(t) and Ca(t)

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Overview

Spatial perfusion measurement techniques

• Single Photon Emission Computer Tomography (SPECT)

• Positron Emission Tomography (PET)

• Xenon-enhanced Computer Tomography (XeCT)

• Dynamic Perfusion Computer Tomography (dynamic PCT)

• Magnetic Resonance Imaging (MRI)

• Dynamic contrast-enhanced perfusion measurement (DCE)

• Dynamic susceptibility contrast perfusion measurement (DSC)

• Arterial spin labeling (ASL)


Single Photon Emission Computer Tomography (SPECT)

Imaging: based on gamma emission of radioactive isotopes

Tracer: 133Xenon (low energy gamma emitter ￫￫￫￫ limited spatial resolution)99mTc-HMPAO), 99mTc-Bicisate (ethyl cysteine dimer [ECD])123I inosine–5-monophosphate (123I-IMP)

Method: Steady-State (Kety-Schmidt-Model)

Measurement time: 10-15 minutes

Spatial resolution: 4-6 mm

Radioactive dose of tracer: 4-13 mSv

Major advantages: bedside use possible

reproducible results

Major drawbacks: radioactive tracer

limited spatial resolution


Positron Emission Tomography (PET)

Imaging: based on beta+ emission of radioactive isotopes

Tracer: based on 15O (15O2, C15O2, and H215O), half life of 2 minutes

substituting blood water

Method: Steady-state (Kety-Schmidt-Model), more complex analysis by

repeated measurement within 1 hour

estimation of arterial input using blood samples

Measurement time: H215O: 1-2 minutes, C15O2: 8-10 minutes


Radioactive dose of tracer: 1-2 mSv per scan

Major advantages: gold-standard

parameter maps

Major drawbacks: radioactive tracer

need for blood samples

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Xenon-enhanced Computer Tomography (XeCT)

Imaging: tracer concentration acquired by attenuation of X-rays (conv. CT)

Tracer: Xenon gas

Method: Steady-state (Kety-Schmidt-Model),

estimation of arterial input using end-tidal Xenon

Measurement time: 6 scans within 4-5 minutes

Spatial resolution: 4 mm

Radiation dose of scan: 3.5-10 mSv

Major advantages: no radioactive tracer

relatively fast

Major drawbacks: ionizing radiation

flow increase due to Xe

no FDA approval of Xe


Dynamic Perfusion Computer Tomography (dynamic PCT)

Imaging: tracer concentration acquired by attenuation of X-rays (conv. CT)

Tracer: iodinated contrast agent

Method: Bolus-tracking (Meier-Zierler-Model)

arterial input function measured from acquired data

Measurement time: continous scanning over 40-50 seconds


Radiation dose of scan: 2 mSv

Major advantages: no radioactive tracer

parameter maps

Major drawbacks: ionizing radiation

limited spatial coverage

Overview


• Single Photon Emission Computer Tomography (SPECT)

• Positron Emission Tomography (PET)

• Xenon-enhanced Computer Tomography (XeCT)

• Dynamic Perfusion Computer Tomography (dynamic PCT)

• Magnetic Resonance Imaging (MRI)

• Dynamic contrast-enhanced perfusion measurement (DCE)

• Dynamic susceptibility contrast perfusion measurement (DSC)

• Arterial spin labeling (ASL)

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Magnetic Resonance Imaging (MRI)

Dynamic contrast enhanced perfusion measurement (DCE)

steady-state method

Dynamic susceptibility perfusion measurement (DSC)

tracking of contrast agent bolus

Arterial spin labeling (ASL)

based on magnetically labeled blood water spins


Dynamic contrast enhanced MRI (DCE-MRI) • Slow injection of Gd-DTPA

• Sampling of signal curve over longer period of time (~10min)

• Observe signal enhancement (T1-effect)

• High spatial resolution

• Mainly used for perfusion estimation outside of brain

• Suitable to estimate exchange parameter with tissue

-50-50

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00 22 44 66 88 1010 1212 1414

Enha

ncem

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%]

Enha

ncem

ent [

%]

Time [min]Time [min]

Enhancement Curves for DCE-MRIEnhancement Curves for DCE-MRI

Enhancing lesionEnhancing lesionVessel/ArteryVessel/Artery

Normal tissueNormal tissue-50

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Enhancement Curves for DCE-MRI

Enhancing lesionVessel/Artery

Normal tissueData: Courtesy, Lars Gerigk

German Cancer Research Center (DKFZ)


Dynamic contrast enhanced MRI (DCE-MRI)

Major drawbacks: limited repeatability

not quantitative

Imaging: high resolution 2D and 3D T1-weighted imaging (e.g. flash)

mainly non-neuro application

Tracer: Gadolinium (Gd) based complex

Method: steady state (multi-compartment model,

non-linear modelling of data

Measurement time: 5-10 minutes

Temporal resolution: 20 seconds


Major advantages: no ionizing radiation

multiple parameter maps

mx.nthu.edu.tw/~tsunghan/images/dcemri.jpg

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Dynamic susceptibility contrast MRI (DSC-MRI)

© Thieme and Schering

• Rapid injection of bolus Gd-DTPA (0.1 or 0.2 mmol/kg)

• Dynamic imaging during first pass

• Observe negative enhancement (T2* effect) using EPI or GE sequence

64 yrs, acute stroke GE-EPI: Transient signal drop as the contrast agent passes through the brain.


Dynamic contrast-enhanced MRI (DCE-MRI)

© Thieme and Schering

rCBVrCBF

TTP FWHMBAT

MTT(CBV/CBF)


Dynamic susceptibility contrast MRI (DSC-MRI)

Imaging:susceptibility-weighted (T2*-contrast) imaging,

mainly neuro-application

Tracer: Gadolinium (Gd) based complex (e.g. Gd-DTPA, GD-BOPTA, …)

Method: bolus tracking (Meier-Zierler-Model),

arterial input function measured from acquired data

Measurement time: 1 minutes

Temporal resolution: 2 seconds



multiple parameter maps

Major drawbacks: limited repeatability

not quantitative

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Micro-vascular

perfusion

Macro-vascular

blood flow

(Angiography)

Time-resolved

macro-vascular

blood flow


Arterial Spin Labeling (ASL)

95% - 97%

3% - 5%

Introdcution

• labeling decays with T1 of blood• micro-vascular perfusion occupies

only small portion of voxel

Problem:

Principle: • magnetic tagging of blood

• imaging downstream

Arterial Spin Labeling (ASL)

0

50

100

150

0 500 1000 1500 2000

BAT

CBF

Quantification of pulsed ASL

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Arterial Spin Labeling

Imaging: fast readout module (EPI, b-SSFP, HASTE, 3D-GRASE)

Tracer: magnetically tagged blood

Method: similar to bolus tracking,

indicator dilution theory

Measurement time: 5 seconds is possible, typ. 5 minutes

Temporal resolution: adjustable, e.g. 100 ms

Spatial resolution:3 mm


no tracer injection

flexible technique

Major drawbacks: relatively low SNR

motion-sensitive

Summary

Cerebral perfusion measurement considered standard (esp. DSC in stroke)

DCE measurement, as well (e.g. in breast)

DSC/DCE: robust technique,

available on most MR-scanners,

limited flexibility, contrast media administration needed

limited repeatability

ASL: no injection of contrast agent

provides flexible technique with great potential (esp. at high fields)

can be repeated

no standard on all MR-scanners

still research tool, but close to clinical use

Cerebral blood flow and perfusion

Pros and cons of imaging techniques

Wintermark et al, Stroke 2005

SPECT PET XeCT PCT DSC ASL

Contrast material 133Xe, 99mTc 15O based Xe Ionidated Gd-chelate blood water

Radiation/study 3.5-12 mSv 0.5-2 mSv 3.5-10 mSv 2-3 mSv - -

Data acquisition 10-15 min 5-9 min 10 min 40 sec 1 min 5 min

Acquisition model SS SS SS BT BT BT,SSSS=steady state, BT=bolus tracking

Assessed parameters CBF CBV, CBF, CBF CBV, CBF, CBV, CBF, CBF, BAT,

rOEF, … MTT, TTP MTT, TTP …

Reproducibility 10% 5% 12% 10-15% 10-15% 10%

Spatial resolution 4-6 mm 4-6 mm 4 mm 1-2 mm 2 mm 2 mm

Repeatability 10 min 10 min 20 min 10 min 25 min 0 min

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References on perfusion measurement

Wintermark, M. et al: Comparative Overview of Brain Perfusion Imaging Techniques, Stroke, Sep 2005, e83-e99

Kety, S.: Regional Cerebral Blood Flow: Estimation by Means of Noametabolized Diffusible Tracers: An Overview,

Seminars in Nuclear Medicine, Vol XV, No 4 (Oct), 1985

Kety SS, Schmidt CF. The nitrous oxide method for the quantitative determination of cerebral blood flow in man:

theory, procedure and normal values. J Clin Invest. 1948;27:476–483.

Meier P, Zierler KL. On the theory of the indicator-dilution method for measurement of blood flow and volume. J

Appl Physiol. 1954;6: 731–744.

Østergaard L, Weisskoff RM, Chesler DA, et al. High resolution measurement of cerebral blood flow using

intravascular tracer bolus passages. Part I: Mathematical approach and statistical analysis. Magn Reson Med

1996;36:715–25

JACKSON A, Analysis of dynamic contrast enhanced MRI, The British Journal of Radiology, 77 (2004), S154–S166

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