A CT method to measure hemodynamics in brain tumors: validation and application of cerebral blood flow maps

Abstract

Background and purpose: CT is an imaging technique that is routinely used for evaluating brain tumors. Nonetheless, imaging often cannot show the distinction between radiation necrosis and neoplastic growth among patients with recurrent symptoms after radiation therapy. In such cases, a diagnostic tool that provides perfusion measurements with high anatomic detail would show the separation between necrotic areas, which are characterized by low perfusion, from neoplastic areas, which are characterized by elevated CBF. We attempted to validate a dynamic contrast-enhanced CT method for the measurement of regional CBF in brain tumors, and to apply this method by creating CBF maps.

Methods: We studied nine New Zealand White rabbits with implanted brain tumors. We obtained dynamic CT measurements of CBF, cerebral blood volume (CBV), and permeability surface (PS) from the tumor, peritumor, and contralateral normal tissue regions. In all nine rabbits (two studies per rabbit), we compared CT-derived CBF values with those simultaneously obtained by the standard of reference ex vivo microsphere technique. Using CT, we examined three rabbits to assess the variability of repeated CBF and CBV measurements; we examined the other six to evaluate regional CBF reactivity to arterial carbon dioxide tensions. Finally, CT CBF maps were obtained from a rabbit with a brain tumor during normocapnia and hypocapnia.

Results: We found a significant linear correlation (r = 0.847) between the regional CT-and microsphere-derived CBF values, with a slope not significantly different from unity (0.99+/-0.03, P>.01). The mean difference between regional CBF measurements obtained using both methods did not significantly deviate from zero (P>.10). During normocapnia, tumor had significantly higher CBF, CBV, and PS values (P<.05) than did peritumor and normal tissues. The variability in CT-derived CBF and CBV measurements in the repeated studies was 13% and 7%, respectively. CT revealed no significantly different CBF CO2 reactivity from that determined by the microsphere method (P>.10). The CBF map of tumor regions during normocapnia showed much higher flow than normal regions manifested, and this difference was reduced on the hypocapnia CBF map.

Conclusion: The dynamic CT method presented herein provides absolute CBF measurements in brain tumors that are accurate and precise. Preliminary CBF maps derived with this method demonstrate their potential for depicting areas of different blood flow within tumors and surrounding tissue, indicating its possible use in the clinical setting.

fig 1.

A, Schematic representation of IRF in a tissue with an intact (ie, impermeable to contrast molecules) BBB. B, Schematic representation of an IRF, R(t), in tissue with a permeable BBB. The first plateau reflects the intravascular phase of the contrast material. The second (and much lower) plateau reflects the extravascular phase. The extraction fraction, E, is derived by dividing the second plateau height by the first plateau height.

fig 2.

Examples of dynamic CT-measured contrast-enhancement curves of an artery (line), normal tissue (squares), and tumor (circles) in a rabbit with brain tumor. For clarity, the tissue curves are displayed using a different scale of CT numbers (right axis). Thus, the arterial enhancement curve (left axis) is more than 10 times higher than that of the tumor curve, and 50 times higher than that of the normal tissue curve. Note the higher washout phase of the tumor curve relative to the normal tissue.fig 3. Contrast-enhanced CT image illustrating tumor, peritumor and contralateral normal ROIs found in a rabbit. The radial arteries (RA) are clearly displayed at the bottom of the figure (adjacent to the radial and ulna bones)

fig 4.

Dynamic CT measurements plotted against microsphere measurements of regional CBF (mL/min/100 g) for 54 ROIs (18 ROIs for each tumor, peritumor, and normal tissue) in nine rabbits with brain tumor. A strong correlation was found between these two sets of measurements (r = 0.847). The slope of the regression line (0.99 ± 0.03, P < .001) was not significantly different from unity

fig 5.

CBF maps derived from a rabbit with brain tumor. The CBF values, ranging from low-to-high flow are color-coded from black (0 mL/min/100 g) to blue and green (100 mL/min/100 g) to yellow and red (200 mL/min/100 g). For both PaCO₂ levels, the tumor is clearly delineated by the red and yellow colors. A, Plain (precontrast) CT Image. The following X-ray CT parameters were used to acquire the image: 80 kVp, 80 mA, 10-cm field of view, and 3-mm slice thickness. Hyperdense areas corresponding to the tumor were observed in the right parietal and temporal regions. B, Normocapnia CBF map. CBF in the tumor ranged from 66 to 208 mL/min/100 g, whereas CBF in the contralateral normal hemisphere ranged from 14 to 75 mL/min/100 g. C, Hypocapnia CBF map. The maximum and minimum CBF values in tumor were 56 and 170 mL/min/100 g, whereas the contralateral normal hemisphere showed CBF values ranging from 3 to 43 mL/min/100 g. D, Subtraction of the hypocapnia CBF map from the normocapnia map. The mean global CBF difference was 18.7 mL/min/100 g. Reduction in CBF upon hyperventilation is shown in both tumor and normal tissues. The green circular areas in the center of the brain are cerebral arteries.