DCE/DSC Beyond Perfusion & Permeability
Ben Dickie1

1University of Manchester, United Kingdom

Synopsis

A healthy cerebrovasculature is crucial for meeting the brains ever changing demand for oxygen and nutrients. Aging and many neurodegenerative diseases lead to insidious vascular changes to vessel size, geometry, and blood brain barrier (BBB) integrity. New approaches to the acquisition and analysis of DCE- and DSC-MRI data are providing novel insights into these cerebrovascular abnormalities, aiding understanding of disease mechanisms and helping to identify novel treatment targets.

Target Audience

Imaging scientists and clinicians using DCE-MRI and DSC-MRI to study vascular dysfunction in the aging and diseased brain.

Outcomes

To learn how to use DCE-MRI and DSC-MRI to i) measure vessel geometry and size, ii) measure capillary transit time heterogeneity, and ii) measure trans blood brain barrier water-exchange.

Background

Cerebral small vessel disease and Alzheimer’s disease (AD) lead to vessel narrowing, causing ischemia and microbleeds1. Hypertension causes vascular remodelling, leading to changes in the thickness of vessel walls2. Changes in microvascular flow patterns occur in AD and increase transit time heterogeneity3, a phenomenon that reduces oxygen extraction fraction4. Insidious blood-brain barrier (BBB) damage occurs as a part of normal aging5, and in vascular and AD dementia5,6. This talk provides an update of recent advances in DCE-MRI and DSC-MRI to probe these pathologies in-vivo.

Methods

DCE-MRI and DSC-MRI are becoming established tools for studying blood-brain barrier leakage (Ktrans) and cerebral blood flow (CBF), respectively. The main problems with each of these techniques arise when converting MRI signal to contrast agent concentration. This is most complex for DSC-MRI, as susceptibility effects of the contrast agent depend heavily on vessel geometry and rely on the contrast agent remaining within the vascular pool. Contrast agent leakage across the BBB can alter the T2* relaxivity and introduce T1 effects, biasing CBF estimates. Conversion of T1 to contrast agent concentrations, as required for DCE-MRI, is more straightforward, as calibration factors are well defined, and mostly independent of vascular architecture and tissue microstructure. However, biases in Ktrans are introduced through non-equal tissue and blood T2* relaxivities, and water-exchange7. Adaptations to image acquisition including use of multi-echo8 and multi-flip angle9 data have enabled such effects to be quantified, providing additional physiological information and improving accuracy of Ktrans and CBF estimates. We also discuss modelling of capillary transit time heterogeneity (CTH) using DSC-MRI, and the emerging evidence of the role of CTH on solute transfer across the BBB.

Results

Multi-gradient echo SPGR and EPI readouts have become available on most commercial MRI scanners, and provide a number of benefits to both DSC- and DCE-MRI including:

  • Ability to quantify the effects of contrast agent on both T1 and T2* within a single acquisition.
  • Use of shorter TRs in DSC-MRI, increasing temporal resolution
  • Estimation of r2* in blood and tissue, enabling correction for unequal/inaccurate blood/tissue T2* relaxivity, leakage correction10, and providing new information on vessel geometry11. By further modifying sequences to include a gradient and spin-echo pair, more specific information on average vessel size and vessel size distribution can be gleaned12.

Trans blood-brain barrier water-exchange may be altered in disease, due to breakdown of tight junctions or transporter dysfunction. Of particular interest is the permeability surface area product to water, PSw, which appears to have greater sensitivity to subtle BBB alterations than leakage of gadolinium contrast agents9. Gathering evidence suggests the effects of water exchange on T1 and T2* can been quantified and corrected by fitting an appropriate water exchange model to first-pass13 or equilibration phase data9,13-14. Resulting estimates of blood water residence time (τb) and PSw may be useful markers of metabolism13 and BBB integrity9, respectively.

Significant interest has arisen in measurements of capillary transit time heterogeneity (CTH), as measured using DSC-MRI, due to its potential implications on extraction of solutes across the BBB, including oxygen4. Deconvolution of DSC-MRI tissue concentration curves with an arterial curve is directly related to the distribution of vascular transit times, however estimates are highly sensitive to noise and uncertainties exist of how valid estimates are in the presence of BBB leakage. Modelling approaches to overcome these issues have been proposed, including gamma function modelling of the transit time distribution15 and leakage correction16. Further details will be provided in the talk.

Conclusion

Recent developments in the field of DCE- and DSC-MRI that enable new physiological readouts of cerebrovascular dysfunction were discussed. These new measurements are becoming increasingly relevant due to the role of cerebrovascular disease in understanding the mechanisms underlying dementia.

Acknowledgements

No acknowledgement found.

References

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16. Larsson, Henrik BW, et al. "Brain capillary transit time heterogeneity in healthy volunteers measured by dynamic contrast‐enhanced T1‐weighted perfusion MRI." Journal of Magnetic Resonance Imaging 45.6 (2017): 1809-1820.

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)