Measuring tumor perfusion in control and treated murine tumors: correlation of microbubble contrast-enhanced sonography to dynamic contrast-enhanced magnetic resonance imaging and fluorodeoxyglucose positron emission tomography.

OBJECTIVE: The purpose of this study was to evaluate the ability of dynamic microbubble contrast-enhanced sonography (MCES), in comparison with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET), to quantitatively characterize tumor perfusion in implanted murine tumors before and after treatment with a variety of regimens. METHODS: Seventeen mice with Lewis lung carcinoma implants were categorized to control, radiation therapy alone, antiangiogenic chemotherapy alone, and combined chemoradiation. On day 0 of each treatment regimen, MCES and DCE-MRI of each tumor were performed. On day 5 of treatment, dynamic FDG-PET, MCES, and DCE-MRI were performed. RESULTS: Microbubble contrast-enhanced sonography showed that intratumoral perfusion, blood volume, and blood velocity were highest in the untreated control group and successively lower in each of the treatment groups: radiation therapy alone resulted in a two-thirds reduction of perfusion; antiangiogenic chemotherapy resulted in a relatively larger reduction; and combined chemoradiotherapy resulted in the largest reduction. Microbubble contrast-enhanced sonography revealed longitudinal decreases in tumor perfusion, blood volume, and microvascular velocity over the 5-day course of chemoradiotherapy (all P < .01); conversely, these values rose significantly for the untreated control tumors (P < .01). Dynamic contrast-enhanced MRI showed a smaller and statistically insignificant average decrease in relative tumor perfusion for treated tumors. Dynamic PET revealed delayed uptake of FDG in the tumors that underwent chemoradiotherapy. CONCLUSIONS: Microbubble contrast-enhanced sonography is an effective tool in the noninvasive, quantitative, longitudinal characterization of neovascularization in murine tumor models and is correlative with DCE-MRI and FDG-PET. Microbubble contrast-enhanced sonography has considerable potential in the clinical assessment of tumor neovascularization and in the assessment of the response to treatment.     

Tracer kinetics analysis of dynamic contrast‐enhanced CT and MR data in patients with squamous cell carcinoma of the upper aerodigestive tract: comparison of the results

Purpose: (i) To evaluate the feasibility of tracer kinetics analysis of dynamic contrast‐enhanced (DCE) CT and T2‐weighted MR data of squamous cell carcinoma (SCCA) of the upper aerodigestive tract. (ii) To compare functional parameters derived by both modalities and examine the interchangeability of them as well as the intra‐ and inter‐rater agreement. Materials and methods: Dynamic contrast‐enhanced‐CT and MR images of 23 patients with SCCA were postprocessed using a distributed‐parameter (DP) tracer kinetic model. The evaluated parameters included blood flow (F), intravascular blood volume (v₁), extravascular extracellular blood volume (v₂), intravascular mean transit time (t₁), lag time (t₀), permeability surface area product (PS) and extraction ratio (E). Mean perfusion values, based on region‐of‐interest analysis, of the tumors and the healthy muscle tissue were compared and correlated. Inter‐rater and intra‐rater variability were assessed. Interchangeability of the tumor functional parameters was tested using Pearson’s correlation coeficients and Bland–Altman plots. Results: The mean values in tumor and healthy muscle tissues were significantly different for each modality (0·0001≤P≤0·03). The mean values of all tumor perfusion parameters apart from v₂ and E were significantly different (0·001≤P≤0·009) between the two modalities. The intra‐rater variability was good to very good for all parameters. The inter‐rater variability was moderate to good. Bland–Altman plots of F, t₁, t₀, and v₂ showed moderate interchangeability. There was a proportionality error in v₁ and PS graphs. Conclusion: The estimation of functional parameters in SCCA is feasible using DCE‐CT and ‐MR with a DP model. The parameters are mostly significantly different and the interchangeability of them is limited.     

Measurement of myocardial blood flow by cardiovascular magnetic resonance perfusion: comparison of distributed parameter and Fermi models with single and dual bolus

Background

Mathematical modeling of cardiovascular magnetic resonance perfusion data allows absolute quantification of myocardial blood flow. Saturation of left ventricle signal during standard contrast administration can compromise the input function used when applying these models. This saturation effect is evident during application of standard Fermi models in single bolus perfusion data. Dual bolus injection protocols have been suggested to eliminate saturation but are much less practical in the clinical setting. The distributed parameter model can also be used for absolute quantification but has not been applied in patients with coronary artery disease. We assessed whether distributed parameter modeling might be less dependent on arterial input function saturation than Fermi modeling in healthy volunteers. We validated the accuracy of each model in detecting reduced myocardial blood flow in stenotic vessels versus gold-standard invasive methods.

Methods

Eight healthy subjects were scanned using a dual bolus cardiac perfusion protocol at 3T. We performed both single and dual bolus analysis of these data using the distributed parameter and Fermi models. For the dual bolus analysis, a scaled pre-bolus arterial input function was used. In single bolus analysis, the arterial input function was extracted from the main bolus. We also performed analysis using both models of single bolus data obtained from five patients with coronary artery disease and findings were compared against independent invasive coronary angiography and fractional flow reserve. Statistical significance was defined as two-sided P value < 0.05.

Results

Fermi models overestimated myocardial blood flow in healthy volunteers due to arterial input function saturation in single bolus analysis compared to dual bolus analysis (P < 0.05). No difference was observed in these volunteers when applying distributed parameter-myocardial blood flow between single and dual bolus analysis. In patients, distributed parameter modeling was able to detect reduced myocardial blood flow at stress (<2.5 mL/min/mL of tissue) in all 12 stenotic vessels compared to only 9 for Fermi modeling.

Conclusions

Comparison of single bolus versus dual bolus values suggests that distributed parameter modeling is less dependent on arterial input function saturation than Fermi modeling. Distributed parameter modeling showed excellent accuracy in detecting reduced myocardial blood flow in all stenotic vessels.

Electronic supplementary material

The online version of this article (doi:10.1186/s12968-015-0125-1) contains supplementary material, which is available to authorized users.