PERFUSION AND DYNAMIC CONTRAST ENHANCED MRI

PERFUSION AND DYNAMIC CONTRAST ENHANCED MRIPresented by Dr Fahad Shafi

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.

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

Exogenous Tracer Methods

Dynamic Susceptibility Contrast-enhanced MR Perfusion.

Dynamic Contrast Enhanced MR Perfusion

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

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

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)

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 (R2*) is calculated from signal intensity, and a baseline subtraction method is applied to measured data. (C) Corrected R2* curve after leakage correction

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

Problems with DSC MRI:

Contrast recirculation

Contrast leakage and tissue enhancement Bolus dispersion and the measurement of absolute CBF

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

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;

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

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

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

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

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

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.

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.

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.

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.

APPLICATIONSMR 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.

Brain tumors

Other disordersIn 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

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

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.

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 215 seconds) for up to 5 to 10 minutes.

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

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

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

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.

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.