Magnetic resonance imaging biomarkers for clinical routine assessment of microvascular architecture in glioma

Abstract

Knowledge about the topological and structural heterogeneity of the microvasculature is important for diagnosis and monitoring of glioma. A vessel caliber and type-dependent temporal shift in the magnetic resonance imaging signal forms the basis for vascular architecture mapping. This study introduced a clinically feasible approach for assessment of vascular pathologies in gliomas using vascular architecture mapping. Sixty consecutive patients with known or suspected gliomas were examined using vascular architecture mapping as part of the routine magnetic resonance imaging protocol. Maps of microvessel radius and density, which adapted to the vasculature-dependent temporal shift phenomenon, were calculated using a costume-made software tool. Microvessel radius and density were moderately to severely elevated in a heterogeneous, inversely correlated pattern within high-grade gliomas. Additionally, three new imaging biomarkers were introduced: Microvessel type indicator allowing differentiation between supplying arterial and draining venous microvasculature in high-grade gliomas. Vascular-induced bolus peak time shift may presumably be sensitive for early neovascularization in the infiltration zone. Surprisingly, curvature showed significant changes in peritumoral vasogenic edema which correlated with neovascularization in the tumor core of high-grade gliomas. These new magnetic resonance imaging biomarkers give insights into complexity and heterogeneity of vascular changes in glioma; however, histological validations in more well-defined patient populations are required.

Vascular architecture mapping for early detection of glioblastoma recurrence

“…Additionally, for the VAM approach, a DSC perfusion MRI using an SE-EPI sequence (TR, 1740 msec; TE, 33 msec) was performed in combination with a separate contrast agent (CA) injection. 17,32 Both DSC perfusion examinations were performed with 60 dynamic measurements and administration of 0.1 mmol/kg body weight gadoterate meglumine (Dotarem, Guerbet) as the CA at a rate of 4 mL/sec using an MR-compatible injector (Spectris, Medrad). The first DSC-MRI was obtained by using SE-EPI-DSC perfusion MRI because unwanted CA leakage occurs to a lesser extent with this technique.…”

“…The first DSC-MRI was obtained by using SE-EPI-DSC perfusion MRI because unwanted CA leakage occurs to a lesser extent with this technique. 32 Our strategies to minimize the probability of patient motions and differences in the time to first-pass peak, which may significantly affect the data evaluation, were described previously. 32 Geometrical parameters were chosen that were identical for the 2 DSC perfusion sequences: in-plane resolution of 1.8 × 1.8 mm, slice thickness of 4 mm, 29 slices, and generalized autocalibrating partially parallel acquisition (GRAPPA) factor of 2.…”

“…38 Analysis of VAM data was performed using custommade MATLAB (MathWorks) software. VAM data postprocessing consisted of 4 steps: 1) calculation of maps of microvascular CBV (mCBV) from the SE-DSC perfusion MRI data; 2) calculation of the so-called vascular hysteresis loop (VHL), 32,33 i.e., the ∆R 2,GE versus (∆R 2,SE ) 3/2 diagram, 20,39 via fitting of the first CA bolus curves of both the GE-and SE-DSC perfusion data, respectively, using a previously described gamma-variate function 11 (correction for remaining CA extravasation was performed as described previously); 5,6,32 3) calculation of microvessel density (MVD) and vessel size index (VSI; i.e., the microvessel radius); 18 and 4) calculation of the microvessel type indicator (MTI), which was previously 32 defined as the area of the VHL with the sign of its rotational direction (i.e., a clockwise VHL direction was identified with a plus sign, and a counterclockwise with a minus sign). Based on previous studies, 14,32 a positive MTI value (i.e., clockwise VHL) is associated with a vascular system that is dominated by arterioles, whereas a negative MTI value (i.e., counterclockwise VHL) is associated with venule-and capillary-like vessel components.…”

Development of a Non-invasive Assessment of Hypoxia and Neovascularization with Magnetic Resonance Imaging in Benign and Malignant Breast Tumors: Initial Results

“…New individual magnetic resonance imaging (MRI) techniques which allow a non-invasive, quantitative measurement of hypoxia as well as microvascular vessel caliber and architecture with hitherto unparalleled accuracy have been developed and pioneered in patients with brain cancers [24][25][26]. Advanced quantitative blood oxygenation leveldependent (qBOLD) imaging allows the absolute quantification of the tissue oxygen extraction fraction (OEF), the oxygen metabolic rate (MRO 2 ), and the mitochondrial oxygen tension (mitoPO 2 ) [27].…”

Genetically encoded iron‐associated proteins as MRI reporters for molecular and cellular imaging

“…Superior soft‐tissue contrast, large availability of imaging techniques, variety of contrast mechanisms, multinuclear capability, absence of ionizing radiation (safety), as well as capability for monitoring functional, anatomical and metabolic information enable MRI to stand out. MRI contrast weighting techniques can detect areas of pathology (scar, inflammation), volume loss, complex tissue architecture, chemical exchange within the macromolecular environment, cellular death and inflammation, metabolite concentration, tissue perfusion, and vascularity . Recent advances in MRI reporter gene techniques have enabled in vivo imaging of specific cell populations of interest regarding cell survival, proliferation, migration, and differentiation, which makes MRI a valuable technology among other molecular imaging modalities.…”