Assessment of Blood Hemodynamics by USPIO-Induced R(1) Changes in MRI of Murine Colon Carcinoma

Abstract

The objective of this study is to assess whether ultrasmall superparamagnetic iron oxide (USPIO)-induced changes of the water proton longitudinal relaxation rate (R(1)) provide a means to assess blood hemodynamics of tumors. Two types of murine colon tumors (C26a and C38) were investigated prior to and following administration of USPIO blood-pool contrast agent with fast R(1) measurements. In a subpopulation of mice, R(1) was measured following administration of hydralazine, a well-known blood hemodynamic modifier. USPIO-induced R(1) increase in C38 tumors (DeltaR(1) = 0.072 +/- 0.0081 s(-1)) was significantly larger than in C26a tumors (DeltaR(1) = 0.032 +/- 0.0018 s(-1), N = 9, t test, P < 0.001). This was in agreement with the immunohistochemical data that showed higher values of relative vascular area (RVA) in C38 tumors than in C26a tumors (RVA = 0.059 +/- 0.015 vs. 0.020 +/- 0.011; P < 0.05). Following administration of hydralazine, a decrease in R(1) value was observed. This was consistent with the vasoconstriction induced by the steal effect mechanism. In conclusion, R(1) changes induced by USPIO are sensitive to tumor vascular morphology and to blood hemodynamics. Thus, R(1) measurements following USPIO administration can give novel insight into the effects of blood hemodynamic modifiers, non-invasively and with a high temporal resolution.

Fig. 1

IR-FLASH measurements of the R ₁ relaxation rate in a C26a murine colon carcinoma. The sixteen IR-FLASH images of a C26a murine colon carcinoma (left). Plot of signal amplitudes from a single voxel within the tumor (right). The dashed line indicates the monoexponential fit (R ² = 0.9996)

Fig. 2

Column graph of the changes in the R ₁ relaxation rate following USPIO administration in a C26a and a C38 colon carcinoma. Symbols indicate the values of R ₁ from four repeated measurements performed prior to and following USPIO administration. Prior to USPIO administration, in the example shown here, R ₁ = 0.5467 ± 0.0024 s⁻¹ in the C26a and R ₁ = 0.5791 ± 0.0029 s⁻¹ in the C38. Following USPIO administration, R ₁ = 0.5692 ± 0.0013 s⁻¹ in the C26a and R ₁ = 0.6596 ± 0.0030 s⁻¹ in the C38. In both tumors, the post-USPIO R ₁ is significantly higher than pre-USPIO R ₁

Fig. 3

Column graph of the changes in water proton R ₁ relaxation rate (ΔR ₁) following USPIO administration in the C26a and C38 colon carcinoma. The R ₁ increase in the C38 (ΔR ₁ = 0.072 ± 0.0081 s⁻¹) was significantly larger than in the C26a colon carcinoma (ΔR ₁ = 0.032 ± 0.0018 s⁻¹, P < 0.001). The ΔR ₁ in all C38 colon carcinoma was larger than 0.045 s⁻¹ (dotted line), while the ΔR ₁ in all C26a colon carcinoma was smaller than this value

Fig. 4

RVA maps of the C26a (a) and C38 (b) tumor section. Each pixel represents a 0.23 × 0.23 mm ROI. Maps are scaled to 100% which corresponds to an RVA value of 21%. c and d Detailed photomicrographs of the tumors in a and b, showing the typical vascular structure of the C26a (c) and the C38 (d) colon carcinoma

Fig. 5

Graph of normalized R ₁ prior to USPIO administration (first time point), following USPIO administration (second time point) and 5 min after hydralazine administration (third time point) in three C38 colon carcinomas. Following hydralazine administration, R ₁ decreased in all tumors, indicating a vasoconstriction effect