Dynamic-contrast-enhanced-MRI with extravasating contrast reagent: Rat cerebral glioma blood volume determination

Li, Xin; Rooney, William D.; Várallyay, Csanád; Gahramanov, Seymur; Muldoon, Leslie L.; Goodman, James A.; Tagge, Ian J.; Selzer, Audrey H.; Pike, Martin M.; Neuwelt, Edward A.; Springer, Charles S.

doi:10.1016/j.jmr.2010.07.004

Cited by 51 publications

(62 citation statements)

References 33 publications

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“…Dynamic contrast-enhancement analysis is an established method for imaging gliomas that has been tested in both the clinical setting and animal models. 3,8,19,29 The MR image is basically a snapshot representation of a structure at a given time, whereas dynamic contrast-enhanced MRI is a time-lapse evaluation through a series of temporally sequential images. To increase the information obtained from contrast-enhanced studies, a wide range of dynamic contrast-enhanced T1-weighted imaging sequences, protocols, image processing methods, and interpretation criteria have been developed and evaluated over the last 20 years.…”

mentioning

confidence: 99%

Using intraoperative dynamic contrast-enhanced T1-weighted MRI to identify residual tumor in glioblastoma surgery

Özduman¹,

Yıldız

Di̇nçer

et al. 2014

JNS

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Object The goal of surgery in high-grade gliomas is to maximize the resection of contrast-enhancing tumor without causing additional neurological deficits. Intraoperative MRI improves surgical results. However, when using contrast material intraoperatively, it may be difficult to differentiate between surgically induced enhancement and residual tumor. The purpose of this study was to assess the usefulness of intraoperative dynamic contrast-enhanced T1-weighted MRI to guide this differential diagnosis and test it against tissue histopathology. Methods Preoperative and intraoperative dynamic contrast-enhanced MRI was performed in 21 patients with histopathologically confirmed WHO Grade IV gliomas using intraoperative 3-T MRI. Standardized regions of interest (ROIs) were placed manually at 2 separate contrast-enhancing areas at the resection border for each patient. Time-intensity curves (TICs) were generated for each ROI. All ROIs were biopsied and the TIC types were compared with histopathological results. Pharmacokinetic modeling was performed in the last 10 patients to confirm nonparametric TIC analysis findings. Results Of the 42 manually selected ROIs in 21 patients, 25 (59.5%) contained solid tumor tissue and 17 (40.5%) retained the brain parenchymal architecture but contained infiltrating tumor cells. Time-intensity curves generated from residual contrast-enhancing tumor and their preoperative counterparts were comparable and showed a quick and persistently increasing slope (“climbing type”). All 17 TICs obtained from regions that did not contain solid tumor tissue were undulating and low in amplitude, compared with those obtained from residual tumors (“low-amplitude type”). Pharmacokinetic findings using the transfer constant, extravascular extracellular volume fraction, rate constant, and initial area under the curve parameters were significantly different for the tumor mass, nontumoral regions, and surgically induced contrast-enhancing areas. Conclusions Intraoperative dynamic contrast-enhanced MRI provides quick, reproducible, high-quality, and simply interpreted dynamic MR images in the intraoperative setting and can aid in differentiating surgically induced enhancement from residual tumor.

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confidence: 99%

Using intraoperative dynamic contrast-enhanced T1-weighted MRI to identify residual tumor in glioblastoma surgery

Özduman¹,

Yıldız

Di̇nçer

et al. 2014

JNS

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“…For this, the arterial input function for each animal was derived from selected pixels in the sagittal sinus as previously described ( 37 ). The tumor precontrast T1 value was determined from measurements by using the same fast gradientecho sequence at nine different fl ip angles ranging from 5° to 75°.…”

Section: Experimental Studiesmentioning

confidence: 99%

Improved Perfusion MR Imaging Assessment of Intracerebral Tumor Blood Volume and Antiangiogenic Therapy Efficacy in a Rat Model with Ferumoxytol

Gahramanov¹,

Muldoon²,

Li³

et al. 2011

Radiology

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Purpose:To evaluate the consistency of tumor blood volume measurements and antiangiogenic therapy effi cacy assessments with a low-molecular-weight gadolinium-based contrast agent (GBCA, gadodiamide) versus an iron oxide nanoparticle (ferumoxytol) in the presence or absence of a loading dose of contrast agent before perfusion magnetic resonance (MR) imaging (preload method). Materials and Methods:The protocol was approved by the institutional animal care and use committee. U87MG tumor cells were implanted intracerebrally in 13 rats. All 13 rats underwent 11.75-T MR imaging with gadodiamide (60 m L) 13 days after tumor implantation. The next day, nine rats underwent MR imaging with ferumoxytol (60 m L). Immediately after ferumoxytol imaging, six rats received bevacizumab (45 mg/kg). MR imaging was repeated 48 hours after bevacizumab treatment with gadodiamide and 72 hours after treatment with ferumoxytol. Each study included three consecutive dynamic susceptibility-weighted contrast material-enhanced (DSC) MR acquisitions, which were performed without preload, with single-dose preload, and with double-dose preload. Tumor relative cerebral blood volume (rCBV) was estimated from each DSC MR acquisition. Two-way repeated measures analysis of variance was performed to test for differences between groups with both contrast agents. Results:DSC MR imaging with gadodiamide and without preload showed low rCBV ( Յ 1.75) in nine of the 13 tumors; estimated rCBV increased progressively with both single-and double-dose preloads ( P , .001). Conversely, rCBVs obtained with ferumoxytol were high ( . 1.75) and remained constant with all three acquisitions. The magnitude of rCBV decrease after bevacizumab administration was dependent on the dose of gadodiamide preload, whereas the magnitude of rCBV decrease with ferumoxytol was constant regardless of whether contrast agent preload was used. Conclusion:With GBCA, tumor rCBV can be underestimated without preload and becomes dose dependent with preload correction. Conversely, ferumoxytol provides consistent assessment of tumor rCBV and antiangiogenic therapy effi cacy.q RSNA, 2011

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“…Many studies have emerged in recent years attempting to validate MR imagingbased perfusion imaging as a biomarker of angiogenesis (Online Table 2). [33][34][35][36][37][38][39][40][41] MR imaging can provide information on tumor perfusion by tracking a bolus of an exogenously administered contrast agent or by tracking endogenous magnetically labeled flowing blood. The former includes DCE PWI, which measures the T1 shortening effect of the contrast agent, and DSC PWI, which measures the susceptibility effect of the contrast agent on T2* GRE images.…”

Section: Functional Mr Imagingmentioning

confidence: 99%

“…33,34 To minimize the effect of extravasated contrast in perfusion measurements, one must use an AIF to measure the rate of incoming blood in a nearby supplying artery or a pre-bolus injection. With a 3D equilibrium water-exchange model, it is possible to derive information on tumor blood volume; extravascular space vascular permeability, and K trans .…”

Section: Functional Mr Imagingmentioning

confidence: 99%

“…With a 3D equilibrium water-exchange model, it is possible to derive information on tumor blood volume; extravascular space vascular permeability, and K trans . 33,34 Perfusion parameters of the U87MG rat xenograft were characterized by Li et al 33 by using DCE-PWI after the IV administration of 50 mol/Kg of Omniscan (gadodiamide; Nycomed Amersham, Oslo, Norway). Using an AIF derived from the superior sagittal sinus (a technique previously validated in rats 42 ), the authors were able to estimate CBV, CBF, K trans , and vascular permeability from first-passage T1-weighted DCE-PWI despite extensive extravasation of the contrast agent.…”

Section: Functional Mr Imagingmentioning

confidence: 99%

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MR Imaging Features of High-Grade Gliomas in Murine Models: How They Compare with Human Disease, Reflect Tumor Biology, and Play a Role in Preclinical Trials

Borges¹,

López‐Larrubia²,

Marques³

et al. 2011

AJNR Am J Neuroradiol

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SUMMARY: Murine models are the most commonly used and best investigated among the animal models of HGG. They constitute an important weapon in the development and testing of new anticancer drugs and have long been used in preclinical trials. Neuroimaging methods, particularly MR imaging, offer important advantages for the evaluation of treatment response: shorter and more reliable treatment end points and insight on tumor biology and physiology through the use of functional imaging DWI, PWI, BOLD, and MR spectroscopy. This functional information has been progressively consolidated as a surrogate marker of tumor biology and genetics and may play a pivotal role in the assessment of specifically targeted drugs, both in clinical and preclinical trials. The purpose of this Research Perspectives was to compile, summarize, and critically assess the available information on the neuroimaging features of different murine models of HGGs, and explain how these correlate with human disease and reflect tumor biology.ABBREVIATIONS: AIF ϭ arterial input function; ATP ϭ adenosine triphosphate; BOLD ϭ blood oxygen level-dependent; DCE ϭ dynamic contrast-enhanced; DSC ϭ dynamic susceptibility contrast; FLASH ϭ fast low-angle shot; gadolinium-DTPA ϭ gadolinium-diethylene-triamine pentaacetic acid; GEMM ϭ genetically engineered mouse model; GRE ϭ gradient recalled-echo; HGG ϭ high-grade glioma; MMP2 ϭ matrix metalloproteinase type 2; MVD ϭ mean vascular density; rCBVϭ relative cerebral blood volume; VEGF ϭ vascular endothelial growth factor A nimal models of HGG have become an imperative tool in the development and testing of new anticancer drugs. The combination of these advanced neuroimaging methods provides a novel integrated environment in which a collection of noninvasive biomarkers validated on well-defined animal models may provide important clues to tumor biology and response to treatment, with potential applications in human neoplasms. In general, the use of animal models overcomes many of the limitations found in the clinical setting, including impracticable serial tissue sampling and difficulties in establishing correlations between tumor physiopathology and its genetic profile, a circumstance limiting considerably the successful implementation of tailored personalized cancer treatments.Among neuroimaging methods, MR imaging is the most common technique to assist the management of patients with brain tumors; it is free of ionizing radiation, overall well-tolerated, and provides detailed anatomic and functional information. Neuroimaging features of murine models of HGG have been less explored due to technical limitations. Highresolution MR imaging of small animals requires high-field magnets with small bores and dedicated coils, adequate anesthesia, and tailored fixation devices (Fig 1).Murines are the most commonly used and are the best investigated models of human glioma. They are easy to handle, have a short life span, and develop central nervous system tumors that are similar to their human counterparts.1,2 Moreover, t...

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Dynamic-contrast-enhanced-MRI with extravasating contrast reagent: Rat cerebral glioma blood volume determination

Cited by 51 publications

References 33 publications

Using intraoperative dynamic contrast-enhanced T1-weighted MRI to identify residual tumor in glioblastoma surgery

Using intraoperative dynamic contrast-enhanced T1-weighted MRI to identify residual tumor in glioblastoma surgery

Improved Perfusion MR Imaging Assessment of Intracerebral Tumor Blood Volume and Antiangiogenic Therapy Efficacy in a Rat Model with Ferumoxytol

MR Imaging Features of High-Grade Gliomas in Murine Models: How They Compare with Human Disease, Reflect Tumor Biology, and Play a Role in Preclinical Trials

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