Imaging vascular function for early stage clinical trials using dynamic contrast-enhanced magnetic resonance imaging

Abstract

Many therapeutic approaches to cancer affect the tumour vasculature, either indirectly or as a direct target. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has become an important means of investigating this action, both pre-clinically and in early stage clinical trials. For such trials, it is essential that the measurement process (i.e. image acquisition and analysis) can be performed effectively and with consistency among contributing centres. As the technique continues to develop in order to provide potential improvements in sensitivity and physiological relevance, there is considerable scope for between-centre variation in techniques. A workshop was convened by the Imaging Committee of the Experimental Cancer Medicine Centres (ECMC) to review the current status of DCE-MRI and to provide recommendations on how the technique can best be used for early stage trials. This review and the consequent recommendations are summarised here. Key Points • Tumour vascular function is key to tumour development and treatment • Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumour vascular function • Thus DCE-MRI with pharmacokinetic models can assess novel treatments • Many recent developments are advancing the accuracy of and information from DCE-MRI • Establishing common methodology across multiple centres is challenging and requires accepted guidelines.

Assessment of Progression-Free-Survival in Glioblastomas by Intratreatment Dynamic Contrast-Enhanced MRI

“…Fitting a model-based function to the measured input function is more stable as it smoothes the data in a way that is constrained to produce realistic input functions, and parameter estimates tend to be more accurate if the input function is appropriate [13]. The DCE-MRI parameters have the following measurement units: K trans in min − 1 ; v e in %; IAUGC in mM · s [14].…”

“…This can be vulnerable to fit failures in the case of highly vascular regions, very poorly perfused regions or physiological motion [23]. Though the relationship between IAUGC and underlying physiology is complex and undefined due to the capture of data from the entire uptake and washout curve [24,25], IAUGC has been proposed as a primary endpoint in studies employing pharmacokinetic MR analysis [25,14]. IAUGC reflects tracer kinetics determined by a combination of blood flow, blood volume, endothelial permeability and interstitial volume [26], yet, both IAUGC and K trans can be used to derive a 'vascularised tumour volume' by counting the voxels with values above a predetermined threshold [25].…”

The Evolution of Ultrasound Technologies; from Anatomic to Physiologic,Histologic, and Molecular Imaging

“…Recently, dynamic contrast enhanced (DCE) MRI and CT has been utilized to evaluate perfusion/permeability and vascular physiology [2]. However, this capacity has not been available for ultrasound.…”

Standardising measurement of tumour vascularity by imaging: recommendations for ultrasound, computed tomography, magnetic resonance imaging and positron emission tomography

“…This issue embraces four seminal articles [1][2][3][4] reviewing how functional information can be accurately, repeatedly and noninvasively collected from cross-sectional imaging techniquesusing ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). This information can be used to assess factors related to the vascularity of a tumour and provide prognostic information and also the likely response to various therapeutic agents.…”

“…The third paper, by Leach et al [3], is perhaps the most complex: "Evaluating vascular function for early stage clinical trials using dynamic contrast enhanced magnetic resonance imaging". It concludes by stating that recent technological advances in MRI provide interesting physiological information in a wide range of clinical and experimental situations.…”