The ability of BLI to quantitate in vivo tumor burden in an orthotopic animal model was investigated through in vivo measurements of both the tumor volume and photon emission from the same group of animals over time. A time series of transverse T2-weighted MR images of a representative tumor-bearing rat brain demonstrates the growth of a 9LLuc tumor, which appears as a hyperintense lesion in the right forebrain (). Corresponding BL images of the same animal, displayed as a pseudocolor image overlaid on a gray scale reference image of the rat head, reveal an intense signal arising from the tumor (). Scatter of tumor-emitted photons as they pass through the brain, bone, and skin likely account for the BL pseudocolor image exceeding the tumor dimensions as measured by MRI. Over time, the bioluminescence signal from the tumor increased in both apparent diameter and intensity as the tumor volume, as measured by MRI, increased. The detected luminescent signal at each time point was quantified and plotted against the corresponding MRI-determined tumor volume for each of the five sham-treated animals. Linear regression analysis revealed an excellent correlation (r=0.91) between the measurement of intracerebral tumor burden using these two imaging modalities ().
Figure 1 Kinetics of intracranial glioma growth in a representative animal. 9LLuc cells were implanted intracerebrally at 16 days before sham treatment with ethanol vehicle and tumor progression was monitored with MRI (A) and BLI (B). The days, post-sham treatment, (more ...)
Quantitation of therapeutic efficacy was accomplished on a separate group of rats with intracerebral 9LLuc
tumors, which were treated with the chemotherapeutic agent BCNU. MR and BL images of a representative animal from this experiment are shown in and B
, respectively. The first images were acquired within 2 hours of BCNU administration followed by repeat scans acquired at selected posttreatment intervals. The MR images revealed that the tumor continued to expand up to 8 days after treatment followed by regression and subsequent regrowth. The corresponding BL images revealed parallel changes in detected photon emission over this same time period. Similar results were observed for the other four animals in the BCNU-treatment group. A plot of tumor volume and detected photon counts versus time for this animal is shown in along with an exponential fit of the tumor regrowth data. Extrapolation of the tumor regrowth back to the time of treatment, allowed for quantitation of cell kill in each animal studied, as previously described [9
]. Mean log cell kill values determined by MRI and BLI were 1.78±0.36 (n
=5 animals) and 1.84±0.73 (n
=5 animals), respectively (), indicating that these two independent imaging methods were statistically identical (P
=.951). The BCNU-induced tumor cell kill resulted in a statistically significant increase (P
=.007) in the survival of the treated animals (41.0±0.7 days) compared with the controls (25.2±7.2 days) as shown in .
Figure 2 Temporal analysis of the response of a 9LLuc tumor to BCNU chemotherapy. Tumor cells were implanted 16 days before treatment. Tumor volume was monitored with T2-weighted MRI (A) and intratumoral luciferase activity was monitored with BLI (B). The days (more ...)
Figure 3 Kaplan-Meier survival analysis of 1xLD10 BCNU-treated (■) and sham-treated control (●) animals. The mean survival times were 41.0±0.7 and 25.2±7.5 days, respectively, for the treated and control groups (mean±SEM, (more ...)