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Simultaneous mapping of blood volume and endothelial permeability surface area product in gliomas using iterative analysis of first-pass dynamic contrast enhanced MRI data

¹ Division of Imaging Science and Biomedical Engineering, Stopford Medical School, University of Manchester, Manchester M13 9PT and ² AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK

View larger version (45K): [in a new window]   Figure 1. Flowchart showing the algorithmic treatment of the data to derive maps of blood volume and permeability. A more detailed description of the automatic decomposition of intravascular and extravascular contrast agent concentration curves is shown in the enlargement to the right. Definitions of abbreviations can be found in Table 2.

View larger version (13K): [in a new window]   Figure 2. Plasma contrast agent concentration–time course (Cp(t)) curves measured from superior sagittal sinus (SSS) in a patient with an anaplastic astrocytoma (case 3) and derived leakage profiles (LPs) on day 0 and day 2. (a) Cp(t) curves sampled with a time interval of 5.05 s between each dynamic phases on day 0 () and day 2 (). Cp(t) data are fitted with variate functions. Bolus arrival time in the SSS on day 0 is 4.45 s earlier than on day 2. In addition, the Cp(t) curve acquired on day 0 is slightly narrower than on day 2 (full width at half height on day 1: full width at half height on day 2=10.14 s:12.11 s) with a higher peak value. The variate functions are concatenated with a straight horizontal line. The height of this line represents the level of a steady state of contrast agent concentration in plasma after recirculation. (b) LPs on day 0 (solid line) and day 2 (dashed line) are calculatd from the two concatenated variate functions. The difference between areas under these two curves is small (Cp(t)day 0:Cp(t)day 2=150.29:147.73).

View larger version (77K): [in a new window]   Figure 3. Trans-axial images from a patient with an anaplastic astrocytoma, acquired on day 0 (top) and day 2 (bottom). (a) T1 weighted images in a contrast enhanced dynamic series 41 s after contrast agent (CA) bolus injection, approximately at the beginning of first recirculation of the CA bolus to the sagittal sinus. (b) Colour rendered volume transfer constant between blood plasma and interstitial tissue (kfp) maps. Dark blue, kfp=0-0.05 min-1; green, kfp 0.05-0.10 min-1; red, kfp 0.10–0.17 min-1; yellow, kfp 0.17–0.25 min-1. (c) Normalized relative cerebral blood volume calculated from T1 weighted dynamic images and corrected for contamination by CA leakage () (equal to , where Cp(t) is the plasma CA concentration–time course curve and was measured from superior sagittal sinus). Dark blue, normalized ; green, normalized ; red, normalized ; yellow, normalized . (d) Relative cerebral blood volume calculated from T2* weighted images (rCBVT2) maps. Dark blue, rCBVT2=0-1.9 A.U.; green, rCBVT2=1.9-2.3 A.U.; red, rCBVT2=2.3-4.1 A.U.; yellow, rCBVT2=4.1-6.5 A.U. A.U. is a unit of normalized rafe of change of Iq* (R2*). rCBVT2=R2*(t)/R2*normal brain(t), where R2*normal brain(t) was measured from the hemisphere contralateral to the tumour, excluding cerebrospinal fluid. (a) There is marked enhancement of the astrocytoma (arrow) and blood vessels (arrowheads) and choroid plexus. The tumour and choroid plexus are best distinguished in the permeability maps (b) owing to high kfp values. Since normal brain tissue with intact brain–blood barrier is not permeable to gadodiamide, both normal brain tissue and blood vessels have low kfp values. Large blood vessels are clearly depicted on the blood volume maps (c). On the normalized maps, the grade III glioma shows heterogeneous increases of blood volume (yellow, red and green representing tumour blood volume ranging from 0.06 to 0.14). Maps of (c) and (d) rCBVT2, show close agreement in appearance, although blood vessels are slightly narrower on maps.

View larger version (28K): [in a new window]   Figure 4. Frequency distributions (histograms) of voxel values of the volume transfer between blood plasma and interstitial tissue (kfp) (upper row) and relative cerebral blood volume calculated from T1 weighted dynamic images and corrected for contamination by contrast agent (CA) leakage () (bottom row) in five gliomas measured on day 0 (solid line) and day 2 (dashed line). One-sided significance levels (p) from the Wald–Wolfowitz runs tests are also given for each pair of histograms. There is no significant difference between the repeated measurements of kfp or in any subject (p>0.05). C.U. is a unit of accumulated CA concentration (mmol xs l-1).

View larger version (34K): [in a new window]   Figure 5. Scatter diagrams of day 0 plotted against day 2 for (a) mean volume transfer blood plasma and interstitial tissue (kfp), (b) the 97.5 percentile of kfp, (c) mean relative cerebral blood volume calculated from T1 weighted dynamic images and corrected for contamination by contrast agent leakage () and (d) the 97.5 percentile of , measured from five gliomas. Intra-class correlation coefficients (r1) were calculated for each pair of repeated measurements on day 0 and day 2. *, Grade III anaplastic astrocytoma (GIII); , Grade VI glioblastoma multiforme (GM). Line of identity (solid line): day 0=day 2. C.U. is a unit of accumulated contrast agent concentration (mmol x s l-1).