A theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast MRI

Digernes, Ingrid; Bjørnerud, Atle; Vatnehol, Svein Are Sirirud; Løvland, Grethe; Courivaud, Fredric A A; Vik-Mo, Einar O.; Meling, Torstein R.; Emblem, Kyrre E.

doi:10.1177/0271678x17694187

Cited by 24 publications

(28 citation statements)

References 37 publications

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“…Finally, using a best fit approach, the area of the vortex is computed and can be normalized by the length of the long axis to account for variations in blood volume fraction. Several physiologic parameters influence these vortex parameters and their biophysical basis is still under investigation (Digernes et al, 2017). Figure 6 shows example VAI based vortex curves along with representative parameters in a glioblastoma patient.…”

Section: Vessel Architectural Imagingmentioning

confidence: 99%

Imaging vascular and hemodynamic features of the brain using dynamic susceptibility contrast and dynamic contrast enhanced MRI

2019

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In the context of neurologic disorders, dynamic susceptibility contrast (DSC) and dynamic contrast enhanced (DCE) MRI provide valuable insights into cerebral vascular function, integrity, and architecture. Even after two decades of use, these modalities continue to evolve as their biophysical and kinetic basis is better understood, with improvements in pulse sequences and accelerated imaging techniques and through application of more robust and automated data analysis strategies. Here, we systematically review each of these elements, with a focus on how their integration improves kinetic parameter accuracy and the development of new hemodynamic biomarkers that provide sub-voxel sensitivity (e.g., capillary transit time and flow heterogeneity). Regarding contrast mechanisms, we discuss the dipole-dipole interactions and susceptibility effects that give rise to simultaneous T, T and T relaxation effects, including their quantification, influence on pulse sequence parameter optimization, and use in methods such as vessel size and vessel architectural imaging. The application of technologic advancements, such as parallel imaging, simultaneous multi-slice, undersampled k-space acquisitions, and sliding window strategies, enables improved spatial and/or temporal resolution of DSC and DCE acquisitions. Such acceleration techniques have also enabled the implementation of, clinically feasible, simultaneous multi-echo spin- and gradient echo acquisitions, providing more comprehensive and quantitative interrogation of T, T and T changes. Characterizing these relaxation rate changes through different post-processing options allows for the quantification of hemodynamics and vascular permeability. The application of different biophysical models provides insight into traditional hemodynamic parameters (e.g., cerebral blood volume) and more advanced parameters (e.g., capillary transit time heterogeneity). We provide insight into the appropriate selection of biophysical models and the necessary post-processing steps to ensure reliable measurements while minimizing potential sources of error. We show representative examples of advanced DSC- and DCE-MRI methods applied to pathologic conditions affecting the cerebral microcirculation, including brain tumors, stroke, aging, and multiple sclerosis. The maturation and standardization of conventional DSC- and DCE-MRI techniques has enabled their increased integration into clinical practice and use in clinical trials, which has, in turn, spurred renewed interest in their technological and biophysical development, paving the way towards a more comprehensive assessment of cerebral hemodynamics.

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Section: Vessel Architectural Imagingmentioning

confidence: 99%

Imaging vascular and hemodynamic features of the brain using dynamic susceptibility contrast and dynamic contrast enhanced MRI

2019

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“…Using these data, the normalized ratio of tumor-to-reference tissue vortex area and vessel size (“vessel size index”) were calculated. The vortex area is a composite parameter reflecting the voxel-wise relative difference between arteriole-to-venule dominance and their oxygen saturation levels 16 .…”

Section: Methodsmentioning

confidence: 99%

Probing tumor microenvironment in patients with newly diagnosed glioblastoma during chemoradiation and adjuvant temozolomide with functional MRI

Vakulenko‐Lagun

Emblem

et al. 2018

Sci Rep

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Functional MRI may identify critical windows of opportunity for drug delivery and distinguish between early treatment responders and non-responders. Using diffusion-weighted, dynamic contrast-enhanced, and dynamic susceptibility contrast MRI, as well as pro-angiogenic and pro-inflammatory blood markers, we prospectively studied the physiologic tumor-related changes in fourteen newly diagnosed glioblastoma patients during standard therapy. 153 MRI scans and blood collection were performed before chemoradiation (baseline), weekly during chemoradiation (week 1–6), monthly before each cycle of adjuvant temozolomide (pre-C1-C6), and after cycle 6. The apparent diffusion coefficient, volume transfer coefficient (Ktrans), and relative cerebral blood volume (rCBV) and flow (rCBF) were calculated within the tumor and edema regions and compared to baseline. Cox regression analysis was used to assess the effect of clinical variables, imaging, and blood markers on progression-free (PFS) and overall survival (OS). After controlling for additional covariates, high baseline rCBV and rCBF within the edema region were associated with worse PFS (microvessel rCBF: HR = 7.849, p = 0.044; panvessel rCBV: HR = 3.763, p = 0.032; panvessel rCBF: HR = 3.984; p = 0.049). The same applied to high week 5 and pre-C1 Ktrans within the tumor region (week 5 Ktrans: HR = 1.038, p = 0.003; pre-C1 Ktrans: HR = 1.029, p = 0.004). Elevated week 6 VEGF levels were associated with worse OS (HR = 1.034; p = 0.004). Our findings suggest a role for rCBV and rCBF at baseline and Ktrans and VEGF levels during treatment as markers of response. Functional imaging changes can differ substantially between tumor and edema regions, highlighting the variable biologic and vascular state of tumor microenvironment during therapy.

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“…DSC data from both GE and SE acquisitions were used to generate maps of cerebral blood volume, cerebral blood flow, mean transit time, and a binary mask of normal-appearing brain tissue as previously described. 11 , 12 SE-derived maps represent the microvascular characteristics and maps derived from GE are macrovascular-weighted. 13 Apparent diffusion coefficient maps from diffusion MRI, postcontrast T1-weighted images, FLAIR images, and associated regions of interest (ROIs) were co-registered to the DSC space using normalized mutual information co-registration.…”

Section: Methodsmentioning

confidence: 99%

Brain metastases with poor vascular function are susceptible to pseudoprogression after stereotactic radiation surgery

Digernes

Grøvik

Nilsen

et al. 2018

Advances in Radiation Oncology

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PurposeThis study aimed to investigate the hemodynamic status of cerebral metastases prior to and after stereotactic radiation surgery (SRS) and to identify the vascular characteristics that are associated with the development of pseudoprogression from radiation-induced damage with and without a radionecrotic component.Methods and materialsTwenty-four patients with 29 metastases from non-small cell lung cancer or malignant melanoma received SRS with dose of 15 Gy to 25 Gy. Magnetic resonance imaging (MRI) scans were acquired prior to SRS, every 3 months during the first year after SRS, and every 6 months thereafter. On the basis of the follow-up MRI scans or histology after SRS, metastases were classified as having response, tumor progression, or pseudoprogression. Advanced perfusion MRI enabled the estimation of vascular status in tumor regions including fractions of abnormal vessel architecture, underperfused tissue, and vessel pruning.ResultsPrior to SRS, metastases that later developed pseudoprogression had a distinct poor vascular function in the peritumoral zone compared with responding metastases (P < .05; number of metastases = 15). In addition, differences were found between the peritumoral zone of pseudoprogressing metastases and normal-appearing brain tissue (P < .05). In contrast, for responding metastases, no differences in vascular status between peritumoral and normal-appearing brain tissue were observed. The dysfunctional peritumoral vasculature persisted in pseudoprogressing metastases after SRS.ConclusionsOur results suggest that the vascular status of peritumoral tissue prior to SRS plays a defining role in the development of pseudoprogression and that advanced perfusion MRI may provide new insights into patients' susceptibility to radiation-induced effects.

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A theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast MRI

Cited by 24 publications

References 37 publications

Imaging vascular and hemodynamic features of the brain using dynamic susceptibility contrast and dynamic contrast enhanced MRI

Imaging vascular and hemodynamic features of the brain using dynamic susceptibility contrast and dynamic contrast enhanced MRI

Probing tumor microenvironment in patients with newly diagnosed glioblastoma during chemoradiation and adjuvant temozolomide with functional MRI

Brain metastases with poor vascular function are susceptible to pseudoprogression after stereotactic radiation surgery

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