High‐resolution longitudinal assessment of flow and permeability in mouse glioma vasculature: Sequential small molecule and SPIO dynamic contrast agent MRI

Abstract

The poor prognosis associated with malignant glioma is largely attributable to its invasiveness and robust angiogenesis. Angiogenesis involves host-tumor interaction and requires in vivo evaluation. Despite their versatility, few studies have employed mouse glioma models with perfusion MRI approaches, and generally lack longitudinal study design. Employing a micro-MRI system (8.5T), a novel dual bolus-tracking perfusion MRI strategy was implemented. Using the small molecule contrast agent Magnevist, dynamic contrast enhanced MRI was implemented in the intracranial 4C8 mouse glioma model to determine Ktrans and ve, indices of tumor vascular permeability and cellularity, respectively. Dynamic susceptibility contrast MRI was subsequently implemented to assess both cerebral blood flow and volume, utilizing the macromolecular superparamagnetic iron oxide, Feridex, which circumvented tumor bolus susceptibility curve distortions from first-pass extravasation. The high resolution parametric maps obtained over 4 weeks, indicated a progression of tumor vascularization, permeability, and decreased cellularity with tumor growth. In conclusion, a comprehensive array of key parameters were reliably quantified in a longitudinal mouse glioma study. The syngeneic 4C8 intracerebral mouse tumor model has excellent characteristics for studies of glioma angiogenesis. This approach provides a useful platform for noninvasive and highly diagnostic longitudinal investigations of anti-angiogenesis strategies in a relevant orthotopic animal model.

High-dose estrogen treatment at reperfusion reduces lesion volume and accelerates recovery of sensorimotor function after experimental ischemic stroke

“…T 2 maps were generated as previously described (Ardelt et al, 2012). A dual bolus DCE/DSC perfusion MRI approach was employed as previously described (Pike et al, 2009), employing a single imaging slice centered within the lesion. The DCE protocol employed a fully relaxed Paravision FLASH sequence followed by 400 rapidly acquired FLASH T 1 images as previously described (Ardelt et al, 2012), employing a femoral vein injection of Magnevist (3x diluted, 2.0 μL/g, 0.33 mmol/kg; Berlex Inc., Montville, NJ) during the series.…”

“…The calculation of ratios to contralateral hemisphere employed ROIs that were mirror images of those in the ipsilateral hemisphere, and placed in the contralateral hemisphere. Processing of perfusion MRI data was performed as previously described using the JIM software package (Pike et al, 2009; Tofts et al, 1999). Specifically, calculation of DCE-MRI parameters followed the modified model that includes a blood plasma volume term (vp) (Tofts et al, 1997).…”

Assessment of multiparametric MRI in a human glioma model to monitor cytotoxic and anti‐angiogenic drug effects

“…MRI is routinely employed to estimate tumor volume using anatomic images, but also tumor-associated edema and tumor cellularity using the apparent diffusion coefficient (ADC) of water (10)(11)(12). Moreover, numerous microvascular parameters that appear to be well suited to the assessment of the effect of anti-angiogenic drugs can be estimated using MRI, such as blood volume, blood flow, microvessel diameter and vessel wall permeability (13)(14)(15). A recent example has shown that the extent of vascular normalization, measured by MRI, is predictive of the outcome of anti-vascular endothelial growth factor therapy in glioblastomas (16).…”

Using Single-Channel Blind Deconvolution to Choose the Most Realistic Pharmacokinetic Model in Dynamic Contrast-Enhanced MR Imaging

“…The parameter T c can be estimated using DSC-MRI with a non-diffusible tracer [44]. Radioactive tracers can be used to measure v e [45].…”