Synopsis

Contrast-enhanced MRI methods follow the dynamic passage of exogenous paramagnetic contrast agents to provide perfusion-related parameters, such as cerebral blood volume and cerebral blood flow, or permeability-related parameters, such as the volume transfer constant or extravascular extracellular volume. Perfusion- and permeability-related biomarkers can inform on different, but complementary, aspects related to vascular proliferation and angiogenic processes. Separate acquisitions and contrast injections are typically used to acquire both perfusion (DSC) and permeability (DCE) in patients. More advanced acquisitions involving multiple echoes permit simultaneous assessment of both perfusion and permeability information and may provide new insight into tumor-induced hemodynamic changes.

Highlights

• Perfusion- and permeability-related biomarkers can inform on different, but complementary, aspects related to vascular proliferation and angiogenic processes
• Perfusion is typically assessed with T₂^*-weighted signals using dynamic susceptibility contrast (DSC) MRI; permeability is typically assessed with T₁-weighted signals using dynamic contrast-enhanced (DCE) MRI
• Separate acquisitions and contrast injections are typically used to acquire both DSC and DCE in patients
• More advanced acquisitions involving multiple echoes permit simultaneous assessment of both perfusion and permeability information and may provide new insight into tumor-induced hemodynamic changes

Outcome / Objectives

• Understand the similarities and differences between DSC- and DCE-MRI
• Understand the advantages and potential trade-offs for combined DSC- and DCE-MRI data acquisition

Introduction

Contrast-enhanced MRI (CE-MRI) methods follow the dynamic passage of exogenous paramagnetic contrast agents to provide perfusion-related parameters, such as cerebral blood volume (CBV) and cerebral blood flow (CBF), or permeability-related parameters, such as the volume transfer constant (K^trans) or extravascular extracellular volume (v_e). These parameters are widely used in cancer imaging to assess altered vascular characteristics and angiogenesis. While both CBV and K^trans are often cited for assessing response to anti-angiogenic treatment, they may provide different but complementary information on angiogenesis (1). However, the calculation of both CBV and K^trans typically requires two different scans (as well as two contrast injections). The combination of perfusion and permeability into a single acquisition may form a more complete basis for physiologic analysis of the complex and heterogeneous cancer microenvironment.

Two main categories of CE-MRI methods exist: perfusion-related parameters are assessed using Dynamic Susceptibility Contrast (DSC)-MRI methods that are predominately sensitive to dynamic T₂ and/or T₂^* changes, while permeability-related parameters are assessed using Dynamic Contrast Enhanced (DCE)-MRI methods that are predominately sensitive to T₁ changes. DSC-MRI methods rely on the contrast agent (CA) confinement to the intravascular space to induce strong susceptibility effects, while DCE-MRI methods rely on CA extravasation to induce T₁ relaxation effects in the interstitial space. However, both methods can be adversely impacted by competing relaxation effects; specifically, T₁ leakage effects can prevent reliable estimation of perfusion metrics in DSC-MRI (2), and vascular T₂^* effects can impact quantification of permeability metrics in DCE-MRI (3). While DSC-MRI perfusion metrics and DCE-MRI permeability metrics may individually benefit from the removal of undesirable T₁ (in DSC-MRI) and T₂^* (in DCE-MRI) effects, the ideal sequence would permit quantification of both perfusion and permeability-related parameters. By modifying the pulse sequence to acquire multiple echoes, T₁ and T₂^* effects can be effectively separated, enabling estimation of both perfusion and permeability-related parameters in a single acquisition.

Multi-echo acquisition methods

A dual-echo (or multi-echo) sequence can provide a wider dynamic range of T₁ and T₂^* sensitivities. However, combining DSC and DCE-MRI into a single acquisition involves trade-offs between conflicting demands (Table 1). In particular, achieving sufficient T₁-weighting for adequate concentration sensitivity can be problematic with a DSC-MRI EPI sequence, but achieving adequate temporal and spatial resolution can be problematic with DCE-MRI single-line acquisitions. Early dual-echo implementations involved single-line acquisitions with single slice coverage (4,5). In order to achieve the desired temporal and spatial resolutions, keyhole (4), sliding window (6), or interleaved acquisition methods (7,8) were often utilized. Later dual-echo (and multi-echo) implementations were developed using multi-slice multi-shot EPI, often in combination with parallel imaging to provide adequate scan parameters (2,9,10). Further improvements in temporal and/or spatial resolution may also be achieved through the use of non-Cartesian acquisition strategies (11), multiband excitation (12), and compressed sensing (13). Finally, further advancements in pulse sequence design have led to the ability to simultaneously measure T₂^*, T₂, and T₁ changes using a combined spin- and gradient-echo (SAGE) EPI sequence (14-19). These advancements have enabled the assessment of multiple complex tumor-related features, including vascular and microvascular flow and volume, cellularity, vessel size and architecture, and permeability.

Comparisons between conventional and multi-echo acquisitions have generally been promising. Quarles et al. (20) showed excellent correlation for DCE-MRI metrics of K^trans and v_e between a conventional single-echo acquisition and a multi-echo acquisition. Schmainda et al. (21) found no significant differences between spiral multi-echo rCBV and conventional EPI single-echo rCBV. In addition to the combined assessment of perfusion and permeability, another advantage to combined DSC-/DCE-MRI is the potential to reduce overall contrast agent dose. Overall, a combined approach leverages the advantages of both DSC-MRI and DCE-MRI to provide comprehensive information about tumors, both within the brain (where DSC is typically preferred) and outside of the brain (where DCE is typically preferred). While most of the applications thus far have been in brain tumors, other applications have included abdominal (8), breast (22), and prostate cancer (7).

Acknowledgements

References

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