Validation Studies of Dynamic Contrast Enhanced MRI

There are numerous imaging and modeling strategies available for the application of DCE-MRI. The results of so many studies are difficult to compare due to the wide variety of existing mathematical models, each having their own assumptions and constraints (Tofts 1997). The DCE-MRI approach is widely used to draw inferences into microvascular parameters such as microvascular permeability, blood volume, and tissue perfusion. Confirmed insight into the whereabouts, and amount of the tracer, at the...

Respiratory Motion

A number of potential strategies are available to compensate for the errors introduced by respiratory motion in dynamic contrast enhanced studies of the liver. One potential approach is to minimise the movement by encouraging shallow breathing at rest and further reduce the impact by the acquisition of relatively thick slices, which will be affected to a lesser extent by small respiratory excursions. In practice this is clearly unsatisfactory and although it may be used to generate data from...

Tumour Staging Tumour Volume Determination Multicentricity and Multifocality

An accurate assessment of the primary tumour extent is crucial for deciding the best management for breast cancer patients. It is particularly important when considering the feasibility of breast-conserving surgery as inaccurate assessment could lead to incomplete tumour excision will result in the need for a second surgical procedure or a high rate of recurrence following apparent curative surgery. Unfortunately, clinical examination, mammogra-phy and breast ultrasonography are poor at...

Evaluating Residual Disease

Tumour size is used to assess the volume of residual disease after treatment (either by clinical examination, X-ray mammography or ultrasound). Each of these techniques, however, overestimates the extent of residual disease at the end of treatment (FeldmaN et al. 1986 Helvie et al. 1996 Vinnicombe et al. 1996 Herrada et al. 1997 Fiorentino et al. 2001). Clinical palpation is an imperfect evaluation method because of intervening skin and soft tissue and is unable to distinguish active disease...

MRI Sequence Type

As discussed throughout the chapter, bolus tracking MRI can be performed using different types of MR sequences. The selection of the optimal sequence depends on a compromise between the different (sometimes competing) factors, as well as the particular application, and the tissue under study. This section discusses some of the main issues associated with the selection of the MR sequence for bolus tracking MRI, and their effects on quantification of perfusion As discussed in Sect. 4.1,...

References

Abraham DC, Jones RC, Jones SE, et al. (1996) Evaluation of neoadjuvant chemotherapeutic response of locally advanced breast cancer by magnetic resonance imaging. Cancer 78 91-100 Adams J, Carder PJ, Downey S, et al. (2000) Vascular endothelial growth factor (VEGF) in breast cancer comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen. Cancer Res 60 2898-2905 Ah-See MW, Makris A, Taylor NJ, et al. (2004) Does vascular imaging with MRI predict response to...

Introduction

Approximately one third of the American and European population will develop cancer at some time in their lives. The incidence of cancer increases with age, and among middle-aged people cancer is the single greatest cause of mortality. Currently the major treatment options are surgery, radiotherapy, cytotoxic chemotherapy and hormonal modulation. Despite the tremendous improvements in cancer treatment over the past few decades, survival rates for many Cancer Research UK, Department of Medical...

Monitoring Response to Treatment and Assessing Residual Disease

It is now well established that wide local excision of breast cancer followed by adjuvant breast irradiation gives the same outcome in terms of survival as mastectomy and, as such, breast conservation is the treatment of choice for many women with breast cancer (Fisher et al. 2002). For some women, however, breast conservation is not possible due to the size, position or multifocal multicentric disease. Neoadjuvant chemotherapy (NAC), also termed primary systemic therapy, is chemotherapy...

Categories of Contrast Agents

MRI contrast agents may be divided into four broad categories non-selective, partially selective, targeted, and activated. The most common agents are those of the non-selective group as they are those that are currently used clinically. Often referred to as extracellular fluid (ECF), or extravascular agents, these are typically small molecules ( 500 Da) administered intravenously and leading to both T and T2* shortening. This subcategory of contrast media includes those agents routinely used in...

Characterizing Individual Tumor Biology

Malignant tumors differ from benign lesions in several regards, notably in having a more active recruitment of neovascularity. This acceleration of angiogenesis is essential for the exponential growth and metastasis of the tumor cells (Folkman 1992). Tumor vessels differ from normal tissue vessels by their structural irregularity (abnormal endothelial cell contours and peculiar branching patterns), heterogeneity (flow, diameter, and spacing), and leakiness to macromo-lecular solutes (Jain 1988...

Which Dcemri Parameter to Measure

The use of DCE-MRI merely implies that images will be acquired at defined intervals during the uptake and elimination of a contrast agent. For an effective compound given at the top of the dose-response curve, the radiologist's qualitative assessment may reveal an effect of the drug, but this non-quantitative approach lacks statistical power especially in early trials where effects on the tumour, and on the images, at lower doses may be small. For practical drug development some quantitative...

Hepatobiliary Contrast Agents

Hepatobiliary contrast agents utilise hepatic excretion mechanisms to produce hepatocyte uptake and biliary excretion of paramagnetic ions by binding them to appropriate ligands. Two agents, Mangafo-dipir trisodium (Mn-DPDP, Teslascan) and Gado-benate dimeglumine (Gd-BOPTA, Multihance) are commercially available and a third, gadoxetic acid (Gd-EOB-DTPA, Eovist) is in phase III clinical trials (see Tables 14.1 and 14.2). Mangafodipir is the first manganese complex that has been used as contrast...

Synopsis

For osteosarcoma and for Ewing's family with local disease, the primary clinical problem is predicting the response of the tumor, so that treatment of individual patients, including limb-sparing surgery, can be planned with confidence Fletcher 1997 . For osteosarcoma, clinical investigations with series of lt 35 patients have convincingly demonstrated the ability of DCE-MRI to measure response to preoperative chemotherapy just prior to tumor removal. These findings should be validated by larger...

Angiography

First, it is useful to consider angiography with conventional small molecular contrast media SMCM . For these agents having molecular weights less than 1000 Daltons, there is a fast transendothelial diffusion resulting in a rapidly declining vessel-to-tissue contrast Taupitz et al. 2000 . Bolus tracking is also recommended when using SMCM to ensure that the image acquisitions are obtained with optimal timing, ideally just after the bolus arrives in the vessels Bonk et al. 2000 . However, the...

Assessing Breast Induration Following Radiation Therapy

Fibrosis is assumed to be the usual explanation of palpable induration firmness or hardness in the breast developing several years post-radiotherapy in the absence of features suggesting tumour recurrence. Fibrosis is a well-recognised late consequence of high dose radiotherapy elsewhere in the body, where it contributes to dose-limiting complications and reduced compliance of organs with important elastic properties. Clinico-pathological studies of induration in the early years following...

Pharmacokinetic Analysis

As discussed in Chaps. 1 and 6 pharmacokinetic analyses of T1-weighted DRCE-MRI data have a number of theoretical advantages Tofts et al. 1999 . The use of pharmacokinetic models leads to the derivation of parameters which are independent of the scanning acquisition protocol or any features associated with it. In theory, such parameters should reflect only tissue characteristics supporting the use of these measurements in multicentre studies employing varying image acquisition protocols and...

Simultaneous Mapping of rCBV and Krans from Drcemri

Map Ktrans Tofts

Simultaneous mapping of rCBV and Ktrans from DRCE-MRI is complicated by the synergistic effects of intravascular and extravascular contrast agent on measured signal intensity. Li et al. 2000b Li and Jackson 2003 have described a novel method which uses an initial data decomposition step to derive separate concentration time course data for intravascular and extravascular contrast media. This data decomposition is performed using prior knowledge of the shape of the intravascular contrast...

Quantitative Approaches Using Pharmacokinetic Models

The optimal analysis of DCE-MRI data would be designed to identify specific quantitative physiological parameters which describe the tissue microvascu-lature being observed. We have discussed previously that the distribution of contrast material will be governed by regional blood flow, blood volume, vessel shape and size, endothelial permeability, endothelial surface area, and the size of the EES. In theory an optimal analysis should allow independent assessment of each of these descriptive...

Data Quantification and Limitations

Tracer kinetic principles can be used to provide estimates of relative blood volume rBV , relative blood flow rBF and mean transit time MTT derived from the first-pass of contrast agent through the microcirculation Rosen et al. 1991 Sorensen et al. 1997 Barbier et al. 2001 Fig. 10.2 . These variables are related by the central volume theorem equation BF BV MTT . Quantification of T2 -weighted DCE-MRI and its application for leaky vasculature is discussed in detail elsewhere in this book see...

Enhancement Curve Analysis

A broad range of approaches have been taken to assess the properties of enhancement curves in various tumours Kuhl and SchilD 2000 . Most of these techniques are designed to deal with baseline variations in signal intensity and with the inherent differences in signal intensity that would be observed due to changes in tuning and scaling factors between scanners or even between sessions on the same scanner. Heywang and co-workers 1989 proposed a classification scheme for breast lesions using nor...

Modelling Blood Flow

Equation 9 provides a straightforward model to allow the estimation of the transfer constant, Ktrans, the vascular plasma volume, Vp, and the interstitial space, ve, from a series of concentration values obtained over time. However, as was noted earlier, these approaches rely on the assumption that contrast agent is instantaneously and well-mixed in each of the compartments it occupies this is, in fact, inherent to the definition of a compartmental model . Additionally, there is no term...

Water Exchange

In the discussion above, and indeed in many studies employing dynamic contrast-enhanced MRI in oncology, it has been assumed that tissues contain a single, homogenous, water population with well described MR properties that undergoes simple changes when subjected to a contrast agent. However, experiments from the early days of biomedical MR suggested that the situation is more complex than this Hazlewood et al. 1974 . Water is found in a number of different environments in a biological tissue....

Dynamic MR Acquisition Techniques

Dynamic Relaxivity Contrast Enhanced Mri

There are two generic approaches for the acquisition of dynamic contrast enhanced MRI data. Relaxivity-based methods use T1-weighted acquisitions whilst susceptibility-based techniques use T2 or more commonly T2 -based sequences. Both methods have specific advantages and disadvantages and historically they have tended to be used in different applications. Dynamic susceptibility contrast enhanced MRI DSC-MRI was first used to study the microcirculation of the brain RosEn et al. 1991 ....