basic physics and applications of mr perfusion and dynamic contrast mr

1. Presented by Dr Fahad Shafi

2.  Perfusion refers to the passage of blood from an arterial
supply to venous drainage through the microcirculation.
 perfusion imaging provides hemodynamic information
that complements the anatomic information attainable
with conventional imaging.

3.  Measurement of tissue perfusion depends on the ability to
serially measure concentration of a tracer agent in a target organ
of interest. Exogenous tracers such as iced saline solution,
iodinated radiographic contrast material, and radionuclides have
been used .
 With the advent of MR imaging, exogenous tracer agents, such
as paramagnetic contrast material, and endogenous tracer
agents, such as magnetically labeled blood, have been used

4. Exogenous Tracer Methods
 Dynamic Susceptibility Contrast-enhanced MR
Perfusion.
 Dynamic Contrast Enhanced MR Perfusion

5. Dynamic Susceptibility Contrast-
enhanced MR Perfusion
 Exploits the T2* susceptibility effects of gadolinium,
rather than the T1 shortening effects routinely
associated with contrast enhancement on
conventional imaging.
 Signal loss resulting from passage of the contrast agent
bolus on T2* weighted images can be used to calculate
the change in contrast concentration occurring in each
pixel

7. Image acquisition
 Comfortably positioned.
 Data is acquired by using a fast imaging technique, such as single or multishot echo
planar imaging (EPI) to produce a temporal resolution of approximately 2 seconds.
 The imaging sequence may be gradient echo which will maximize T2* weighting or
alternatively a spin echo approach can be used which will minimize the signal
contribution from large vessels.
 A series of at least five pre-contrast images should be collected prior to the passage of the
bolus to improve the estimation of the signal intensity baseline during analysis.
 A standard contrast dose (0.1 mmol/kg) is adequate in most cases although double dose
of gadolinium (0.2 mmol/Kg) may be used to improve signal to noise ratio.
 The contrast is usually injected via an 18- or 20-gauge IV catheter at a high rate (3-7
mL/sec) using a power injector. The injection should be followed by a saline flush of at
least 25 mL (20-30 mL) in order to ensure that the bolus, which enters the central
circulation is as coherent as possible

8. Data analysis:
 The drop in T2* signal caused by the susceptibility
effects of gadolinium is computed on a voxel-by-voxel
basis and used to construct a time-versus intensity
curve.
 The degree of signal drop is then assumed to be
proportional to the tissue concentration of
gadolinium, so that relative concentration-time curves
can be obtained (delta R2 curves)

9. Figure shows data analysis in DSC perfusion. (A) Time-versus MR signal intensity curve where signal
intensity decrease during passage of contrast agent bolus and is measured from a series of MR
images. (B) Tissue concentration-versus time curve where change in the relaxation rate (ΔR2*) is
calculated from signal intensity, and a baseline subtraction method is applied to measured data. (C)
Corrected ΔR2* curve after leakage correction

10. To obtain tissue response function, arterial concentration-time curve, or
arterial input function, must be deconvolved from measured tissue
concentration-time curve. This arterial input function may be derived directly
from imaging data

11. Problems with DSC MRI:
 Contrast recirculation
 Contrast leakage and tissue enhancement
 Bolus dispersion and the measurement of
absolute CBF

12. Dynamic Contrast Enhanced MR
Perfusion
 provides insight into the nature of the tissue
properties at the microvascular level by demonstrating
the wash-in, plateau, and washout contrast kinetics of
the tissue.
 also referred as ‘permeability’ MRI, is an entirely
different approach to MR perfusion as the main focus
is on estimating tumor permeability

13.  main advantage of T1- based techniques is that tumor
leakiness (enhancement) is used for data analysis
rather than considering it as an artifact as in DSC MRP.
 It has been established that quantification of contrast
leakage can provide powerful indicators of the state of
neovascular angiogenesis in pathologies, such as
tumors and inflammatory tissue;

14. Principle:
 measures the ‘relaxivity effects’ of the paramagnetic
contrast material.
 DCE MRP is based on a two-compartmental (plasma
space and extravascular-extracellular space)
pharmacokinetic model

15. Dynamic contrast-enhanced MR perfusion: Two-compartment model
demonstrates the exchange of contrast between plasma and extravascular-
extracellular space

16. Image acquisition:
 perform baseline T1 mapping, acquire DCE MRP
images, convert signal intensity data to gadolinium
concentration, determine the vascular input function,
and perform pharmacokinetic modeling.
 lower dose of gadolinium is administered (typically a
single dose of 0.1 mmol/kg) at a lower rate (2 mL/sec)
and repetitive acquisitions are then made through the
lesion at longer intervals, typically every 15 to 26
seconds

17. Data analysis:
 Simple analysis techniques: comparing the signal
intensity curves from ROI.
 simplest of these is a measurement of the time taken for
the tumor tissue to attain 90 percent of its subsequent
maximal enhancement (T90).
 Various curve shapes can also provide insight into the
quantification and calculates a standardized slope of the
enhancement curve

18.  Pharmacokinetic analysis techniques: several
metrics are commonly derived: the transfer constant
(ktrans), the fractional volume of the extravascular
extracellular space (ve), the rate constant (kep, kep =
ktrans/ve), and the fractional volume of the plasma
space (vp).
 intended to calculate the biological features, such as
endothelial permeability and the endothelial surface
area, which are relatively independent of imaging
approach

19. Problems with quantitative
measurement of DCE MRI:
 Partial volume averaging effects: excluding any
voxel which produces values over a certain threshold
(1.2/ min) as being vascular in origin or more complex
pharmacokinetic models.
 Long acquisition time: modifying the
pharmacokinetic model and describing only the first
passage of the contrast bolus. This technique also
eliminates the problems with partial volume averaging
described above and produces highly reproducible
parametric maps of both ktrans and CBV.

20.  Flow dependency of ktrans: in areas where there is
contrast leakage and the blood flow is inadequate to
replenish contrast at adequate rate; as a result plasma
contrast concentration decreases and ktrans will
reflect local blood flow.

21. Endogenous Tracer Methods Arterial Spin Labeling MR
Imaging
 Arterial blood flowing towards the region of interest is
tagged by magnetic inversion pulses (proton phase is
changed).
↓
 After a delay to allow for inflow of tagged blood,
image is acquired in slice of interest. This image is
called ‘tag image’.
↓
 Second image without in-flowing tagged blood. This
image is called ‘control image’.

22. ↓
 Tag image is subtracted from control image
↓
 This results into perfusion image representing ‘tagged
blood’ that flowed into the image slice.
 It has poor SNR, however, ASL has better spatial and
temporal resolution than PET. Poor SNR and
sensitivity to abnormally long transit delays of tagged
protons prevents its general application.

24. APPLICATIONS
 MR Perfusion in Stroke
 Mismatch between PW and DW represent potentially
salvageable tissue (penumbra). PW-DW mismatch is
also indicator of clinical outcome. Small mismatch has
good clinical outcome. Large mismatch is associated
with poor clinical outcome and larger vessel occlusion.

28. Brain tumors

30. Other disorders
 In addition to evaluation of ischemia and tumors, MR perfusion
imaging has been applied to the study of various other neurologic and
psychiatric disorders, such as dementia and migraine headaches .

 The effects of psychoactive drugs, such as cocaine, have been studied as
well (Kaufman MJ et al., presented at the International Society of
Magnetic Resonance in Medicine, April 1996).
 In the case of migraine headaches, decreases in cerebral blood volume
and cerebral blood flow have been seen during the auras compared
with the post-aura state (Sorensen AG et al., presented at the
International Society of Magnetic Resonance in Medicine, April 1996).
 In the case of dementia, decreases in cerebral blood volume in the
temporal and parietal lobes of patients with Alzheimer's disease have
correlated well with the results of SPECT studies on the same subjects

31. DYNAMIC CONTRAST-ENHANCED
MRI
 malignant lesions usually show faster and higher levels
of enhancement than normal tissue. This
enhancement pattern of the malignant lesions reflects
increased vascularity (neoangiogenesis) and higher
endothelial permeability to the contrast molecules.
 dynamic contrast-enhanced MRI (DCE-MRI) is
modality of choice for the diagnosis and
characterization of the tumors of the brain, breast,
prostate, liver, cervix and musculoskeletal system

32. Principle:
 relies on fast MRI sequences obtained before, during
and after the rapid intravenous (IV) administration of
a gadolinium-based contrast agent.
 DCE-MRI is sensitive to alterations in vascular
permeability, extracellular space and blood flow. The
DCE-MRI enables the depiction of physiologic
alterations as well as morphologic changes.

33. Image acquisition:
 minimum of three sections
 imaging volume that includes a region outside the tumor,
such as an artery or muscle for normalization.
 injected at a constant rate with a power injector typically
using 3D T1-weighted acquisition.
 Serial image sets are obtained sequentially every 5 seconds
(ranging from 2–15 seconds) for up to 5 to 10 minutes.

34. Data analysis:Qualitative or visual analysis is most readily
accessible analytic but also the least standardized method

35. Semi-quantitative analysis:
 calculates various curve parameters and is also referred
as curveology.
 also based on the assumption of early and intense
enhancement and washout as a predictor of
malignancy.
 Parameters are obtained to characterize the shape of
the time-intensity curve, such as the time of first
contrast uptake, time to peak, maximum slope, peak
enhancement, and wash-in and washout curve shapes

36.  There are three common dynamic curve types after
initial uptake: type 1, persistent increase; type 2,
plateau; and type 3, decline after initial upslope. Type 3
is considered to be indicator of malignancy.
 semiquantitative approach is widely used and has the
advantage of being simple to perform

37.  It has limitations in terms of generalization across
acquisition protocols, sequences, and all other factors
contributing to the MR signal intensity, which in turn
affect curve metrics, such as maximum enhancement
and washout percentage.

38. Quantitative analysis:
 Quantitative analysis is most generalizable but most
complex method.
 It depends on contrast concentration curves over time and
use pharmacokinetic models to calculate permeability
constants.
 fundamental limitation of DCE-MRI, namely the
parameters it generates are inherently ambiguous with
regard to their physiologic significance.