Article Figures & Data
Figures
- Figure 1.
Evaluation of fluid velocity measurements in a flow phantom. A, Photograph of the fluid velocity flow phantom, based on a 5-mL syringe. The black, dashed box shows the approximate location of the imaging plane used. B, Fluid velocity vector field, acquired from a slice through the flow phantom, color coded to reflect the fluid speed, and with the direction characterized using a streamlining algorithm (black lines). C, The average velocity in the center of the phantom is shown plotted against the inflow rate (error bars show the SD in each measurement) for venc ranging from 5,000 to 250 μm/s. A significant linear correlation was measured for venc values of 5,000 and 2,000 μm/s (P < 0.01). At small venc, aliasing was noted at higher inflow rates (arrows) alongside signal crushing (particularly evident at venc = 250 μm/s). Each data point on the graph corresponds to the average value measured in 20 to 30 voxels in the phantom.
- Figure 2.
Evaluation of vascular nulling in tumor xenograft models. A, Example maps showing the nulling ratio (the ratio of images acquired with vascular nulling to one acquired without vascular nulling) in an agar phantom and two different tumors. In the agar phantom, the nulling ratio was zero (top row), as expected due to the absence of flowing fluid. B, A plot of the average nulling ratio as a function of the assumed blood longitudinal relaxation time (T1,blood). The assumed value of T1,blood is used to set the recovery time following the inversion preparation [trec = ln(2) T1,blood]. The graph shows that, for a range of T1,blood of 1,600 to 2,500 ms, the nulling ratio is maximal. At lower values, the nulling is lower as the signal from blood has not recovered to a null point; at larger values, the signal has recovered past the null. The plateau represents a region where the signal from blood is near to or at the null point and has sufficient time to flow into and replace unlabeled blood within the imaging slice.
- Figure 3.
Example convection-MRI data sets (both raw image data and processed image data) in two example LS174T tumor xenografts, representative magnitude (A and H) and phase (B and I) images; maps of the change in phase with velocity-encoding gradients applied in vertical (readout; C and J) and horizontal (phase-encoding; D and K) directions. Velocity vector maps (E and L) show the direction of fluid transport through the tumor interstitium, which is better visualized using a streamlining algorithm (F and M) to connect pathways of coherent fluid convection (bottom row, colored arrows). Streamlines are color coded to reflect the local fluid speed, which is also represented in histograms (G and N).
- Figure 4.
Results of simulations of fluid flow in SW1222 tumors. A, A schematic diagram of the multicompartment simulations (not to scale), in which red tubes represent blood vessels, yellow spheres are cells, and the yellow cuboid represents the imaging slice. Parameters from the numerical simulation are overlaid. B, The mean value of IFV is plotted as a function of the percentage nulling of the interstitial fluid for three simulated velocity values (0.02, 0.05, and 0.1 mm/s). Error bars show the SE in the mean value from 1,000 Monte Carlo simulations. C, IFV plotted against simulated interstitial velocity for four vascular fractional nulling values (100%, 95%, 80%, and 50%). Error bars, SEM.
- Figure 5.
Estimation of effective fluid pressure (Peff) from convection-MRI measurements. A and B, An example convection-MRI fluid velocity streamline map (A) and the corresponding effective pressure map (B) from the same SW1222 tumor. C, Measurements of mean effective fluid pressure with convection-MRI vs. direct measurement of IFP with a pressure transducer. Each point corresponds to the mean pressure in a different tumor; error bars, SE. Convection-MRI and pressure transducer measurements were significantly correlated (P < 0.05, Spearman rho).
- Figure 6.
Comparison of perfusion (measured using ASL) and convection-MRI measurements. A, Perfusion maps in SW1222 tumors (left and right) and an LS174T tumor (center). ASL measurements are shown as heat maps and are overlaid with black streamlines showing the measured path, followed by fluid within tumors. B, Fluid flow measured in vivo with convection-MRI are shown as gray streamlines and perfusion is shown as a color scale. The location of blood vessels is represented by yellow volume renderings, acquired using ex vivo microvascular casting and imaged with micro-CT. Data are shown in example LS174T (left) and SW1222 (right) tumors. In the SW1222 tumor, larger vessel structures in the center of the tumor could be due to swelling by the casting material, although it is unclear if these vessels would have also been swollen under normal physiological conditions. A high-resolution version is provided in Supplementary Fig. S3. C, The relationship between fluid flow, vascular perfusion, and the delivery of a medium molecular weight contrast agent in two LS174T tumors. Left, uptake of Gd-DTPA, an MRI contrast agent; middle, vascular perfusion maps (color scale) overlaid with interstitial convection streamlines (gray); right, effective pressure measurements from fluid mechanical modeling of convection-MRI data. The blue arrow in the top row shows a region between two lobes of the tumor in which the contrast agent preferentially accumulates, interstitial convection streamlines converge, a limited vascular supply is evident, and has a low IFP. In the bottom row, a blue arrow highlights a region with limited contrast agent uptake, a limited vascular supply, and with raised IFP. Both examples show the ability of convection-MRI and ASL, in combination, to identify regions that preferentially accumulate or resist the accumulation of exogenously administered agents. This could potentially be extended to the prediction of the uptake of therapeutic agents.
- Figure 7.
Tumor growth and response to therapy characterized with convection-MRI. A, Example maps of vascular perfusion, effective pressure (Peff), fluid velocity, and ADC during 10 days of growth in two colorectal tumor xenografts (LS174T and SW1222) and at 24 hours following a single dose of the VDA CA4P (100 mg/kg). B, Scatter plots of the mean values of these parameters from the whole tumor cohort. Fluid speed, measured using convection-MRI, tends to increase with tumor volume, while perfusion and Peff decrease. Each point corresponds to a single measurement from a tumor, and black and gray lines connect individual tumors [LS174T (n = 6) and SW1222 (n = 7) colorectal tumor xenografts, respectively]. C, Mean change in each parameter at 24 hours following treatment with CA4P. Tumor volume did not significantly change with treatment, while in LS174T tumors, perfusion decreased and interstitial fluid speed and ADC increased. In SW1222 tumors, perfusion and Peff significantly decreased and ADC significantly increased. Error bars, SEM; *, P < 0.05; **, P < 0.01.
Additional Files
Supplementary Data
- Supplemental Movie 1: Convection-MRI sequence - Supplemental Movie 1: Schematic movie illustrating the physical principles underpinning the convection-MRI sequence
- Supplemental Movie 2: Interstitial convection, vascular perfusion and the location of blood vessels in an LS174T tumor - Supplemental Movie 2: Animated EVAC streamlines (grey lines), showing the path taken by interstitial fluid, overlaid on vascular perfusion measurements (colour scale, measured in vivo using arterial spin labelling) and the location of blood vessels (yellow structures, measured ex vivo using micro-CT). The data were acquired in an LS174T colorectal carcinoma tumour xenograft.
- Supplemental Movie 3: Interstitial convection and vascular perfusion in an LS174T tumor - Supplemental Movie 3: Animated EVAC streamlines (grey lines), showing the path taken by interstitial fluid, overlaid on vascular perfusion measurements (colour scale, measured in vivo using arterial spin labelling) and the location of blood vessels (yellow structures, measured ex vivo using micro-CT). The data were acquired in an LS174T colorectal carcinoma tumour xenograft.
- Supplemental Movie 4: Interstitial convection and vascular perfusion in an SW1222 tumor - Supplemental Movie 4: Animated EVAC streamlines (grey lines), showing the path taken by interstitial fluid, overlaid on vascular perfusion measurements (colour scale, measured in vivo using arterial spin labelling) and the location of blood vessels (yellow structures, measured ex vivo using micro-CT). The data were acquired in an SW1222 colorectal carcinoma tumour xenograft.
- Supplemental Movie 5: Interstitial convection and Gd-DTPA enhancement with time in an LS174T tumor - Supplemental Movie 5: Interstitial convection, measured using EVAC-MRI and animated using a particle simulation (left), compared with MRI signal enhancement with time, following injection with a contrast agent (Gd-DTPA), in an LS174T tumour.
- Supplementary Data - Additional data describing the reproducibility of convectionMRI data, and a figure showing the convectionMRI acquisition sequence.
- Supplemental Figure 3 - High-resolution copy of Figure 6b. Fluid flow measured in vivo with convectionMRI is shown as grey streamlines and perfusion is shown as a colorscale. The location of blood vessels is represented by yellow volume renderings, acquired using ex vivo microvascular casting and imaged with micro-CT.
Volume 78, Issue 7
