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MRI for assessing antivascular cancer treatments

Paul Strickland Scanner Centre, Mount Vernon Hospital, Rickmansworth Road, Northwood, Middlesex HA6 2RN, UK

View larger version (14K): [in a new window]   Figure 1. Body compartments accessed by low molecular weight contrast media.

View larger version (81K): [in a new window]   Figure 2. Typical T2* weighted dynamic contrast-enhanced MRI study in invasive ductal breast cancer. Same patient illustrated in Figures 3–6. 40 ml of intravenous contrast Gd-DTPA was given after the 10th data point. Signal intensity changes for three regions of interest are shown. First pass T2* susceptibility effects cause marked darkening of the tumour with no alteration in signal intensity of normal parenchymal tissue or fat. The first pass and recirculation phases are indicated. Anatomical T2 weighted image and subtraction image of the nadir point for the tumour regions of interest are shown.

View larger version (38K): [in a new window]   Figure 3. Model fitting of T2* weighted data and parametric map formation. Same patient illustrated in Figures 2 and 4–6. T2* signal intensity data from Figure 2 (tumour region of interest) is converted into R2* (1/T2*) and then fitted with a gamma variate function. Parametric maps representing blood flow kinetics (relative blood volume (top), mean transit time and relative blood volume (bottom) are derived on a pixel-by-pixel basis. The computed values of relative blood volume (rBV), relative blood flow (rBF) and mean transit time (MTT) for the whole tumour region of interest are 694, 27.3 arbitrary units and 25.4 s.

View larger version (84K): [in a new window]   Figure 4. Typical T1 weighted dynamic contrast-enhanced (DCE) MRI study. Same patient illustrated in Figures 2, 3, 5 and 6. 20 ml of intravenous contrast Gd-DTPA was given during the 4th data point. Marked enhancement with washout of the breast tumour with curve shape different to normal tissue and fat. The shape of the curve is in marked contrast to that seen on T2* DCE-MRI (Figure 2) for the same regions of interest. Early (48 s minus pre-contrast) and late subtraction (last post-contrast minus pre-contrast) images are also shown.

View larger version (55K): [in a new window]   Figure 5. Superimposing signal intensity data from T1 and T2* weighted dynamic contrast-enhanced (DCE) MRI on the same time-scale. Same patient as illustrated Figures 2–4 and 6. T1 and T2* weighted DCE-MRI curves for the tumour region of interest shown in Figures 2 and 4 are superimposed on the same time scale. The zero point on the time scale represents the point of injection of contrast medium for the respective studies. The onset and short duration of early T2* weighted DCE-MRI effects corresponds precisely to the upslope on the T1 weighted enhancement curve confirming that the upslope has a significant vascular contribution. Transfer constant (Ktrans, colour scale 0–1 min–1) and relative blood flow (rBF) pixel maps are shown. The area of lower transfer constant within the tumour (arrow) corresponds to an area of low relative blood flow.

View larger version (62K): [in a new window]   Figure 6. Converting signal intensity into contrast concentration and model fitting. Data obtained from the patient illustrated Figure 4 for the tumour region of interest. Quantification of signal intensity data () into contrast agent concentration (•) is performed first according to the method described by Parker et al [61]. The model fitting procedure (continuous line) is done using the Tofts' model [81]. Note that model fitting to contrast agent concentration data is not perfect. Calculated quantified parameters are transfer constant=2.31 min–1, leakage space 59%, maximum contrast medium concentration 0.50 mmol l–1). Corresponding transfer constant (Ktrans, colour scale 0–1 min–1) and leakage space (ve, colour scale 0–100%) pixel maps are also shown.

View larger version (86K): [in a new window]   Figure 7. Significant changes in blood oxygenation level dependent (BOLD) signal intensity following antivascular targeting treatment. Axial BOLD spoiled gradient echo MR images (TR=100 ms, TE=60 ms, flip angle=40°) through the mid-pelvis shows a large, left inferior hypogastric lymph node (arrow) in a patient with malignant peritoneal carcinoma. Images were obtained twice before (–5 days and –1 day) and 4 h and 24 h after the first administration of a vascular targeting agent (Combretastatin-A4-phosphate, 52 mg m–2). Darkening within the centre of the lesion at 4 h with treatment is consistent with the presence of reduced blood flow and an increase in the amount of deoxyhaemoglobin. This BOLD effect reverses by 24 h. Corresponding signal intensity time curves are shown which show marked but reversible alteration in contrast agent kinetics.