Open-source versatile 3D-print animal conditioning platform design for in vivo preclinical brain imaging in awake mice and anesthetized mice and rats.

Proper animal conditioning is a key factor in the quality and success of preclinical neuroimaging applications. Here, we introduce an open-source easy-to-modify multimodal 3D printable design for rodent conditioning for magnetic resonance imaging (MRI) or other imaging modalities. Our design can be used for brain imaging in anesthetized or awake mice, and in anesthetized rats. We show ease of use and reproducibility of subject conditioning with anatomical T2-weighted imaging for both mice and rats. We also demonstrate the application of our design for awake functional MRI in mice using both visual evoked potential and olfactory stimulation paradigms. In addition, using a combined MRI, positron emission tomography and X-ray computed tomography experiment, we demonstrate that our proposed cradle design can be utilized for multiple imaging modalities.

Estimation of Contrast Agent Concentration in DCE-MRI Using 2 Flip Angles.

PURPOSE: The aim of this study was to investigate the feasibility of using 2 flip angles (FAs) with an ultrashort echo time during dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) for estimation of plasma gadolinium (Gd) concentration without using a precontrast longitudinal relaxation time T1 (T10) measurement. METHODS: T1-weighted DCE-MRI experiments were carried out with C57BL/6J mice using the scan protocol with 2 FAs over 3 sequential segments during 1 scan. The data with 2 FAs were used to estimate T10 (T1T) during conversion of a time-intensity curve to the time-concentration curve. Three dosages of gadolinium-based contrast agent were used to achieve a wide range of variability in Gd concentrations when measured at 10 minutes postinjection: 0.05 mmol/kg (n = 6), 0.1 mmol/kg (n = 11), and 0.15 mmol/kg (n = 7). For comparison, the signal-to-concentration conversion was also conducted using the T10 measured from the precontrast scan (T1M) as well as a constant T10 (2.1 seconds) from the literature (T1C). The Gd concentrations ([Gd]) estimated using DCE-MRI data for the time of retro-orbital blood collection ([Gd]T1T, [Gd]T1M, and [Gd]T1C, respectively) were compared against the [Gd] of the blood samples measured by inductively coupled plasma mass spectrometry ([Gd]MS). In addition, contrast kinetic model analysis was conducted on mice with GL261 brain tumors (n = 5) using the 3 different methods for T10. RESULTS: T1T strongly correlated with T1M (r = 0.81). [Gd]T1M and [Gd]T1T were significantly different from [Gd]T1C. [Gd]T1M and [Gd]T1T were in good agreement with [Gd]MS with strong correlations (mean percentage error ± standard deviation) of r = 0.70 (16% ± 56%) and r = 0.85 (15% ± 44%), respectively. In contrast, [Gd]T1C had a weak correlation of r = 0.52 with larger errors of 33% ± 24%. The contrast kinetic model parameters of GL261 brain tumors using T1T were not significantly different from those using T1M. CONCLUSIONS: This study substantiates the feasibility of using the 2-FA approach during DCE-MRI scan to estimate [Gd] in the plasma without using an extra scan to perform precontrast T1 measurements.

Changes in oxygenation of intracranial tumors with carbogen: a BOLD MRI and EPR oximetry study.

PURPOSE: To examine, using blood oxygen level dependent (BOLD) MRI and EPR oximetry, the changes in oxygenation of intracranial tumors induced by carbogen breathing. MATERIALS AND METHODS: The 9L and CNS-1 intracranial rat tumor models were imaged at 7T, before and during carbogen breathing, using a multi-echo gradient-echo (GE) sequence to map R(2)*. On a different group of 9L tumors, tissue pO(2) was measured using EPR oximetry with lithium phthalocyanine as the oxygen-sensitive material. RESULTS: The average decline in R(2)* with carbogen breathing was 13 +/- 1 s(-1) in the CNS-1 tumors and 29 +/- 4 s(-1) in the 9L tumor. The SI vs. TE decay curves indicate the presence of multiple components in the tumor. Tissue pO(2) in the two 9L tumors measured was 8.6 +/- 0.5 and 3.6 +/- 0.6 mmHg during air breathing, and rose to 20 +/- 7 and 16 +/- 4 mmHg (mean +/- SE) with carbogen breathing. Significant changes were observed by 10 minutes, but changes in pO(2) and R(2)* continued in some subjects over the entire 40 minutes. CONCLUSION: EPR results indicate that glial sarcomas may be radiobiologically hypoxic. Both EPR and BOLD data indicate that carbogen breathing increases brain tumor oxygenation. These data support the use of BOLD imaging to monitor changes in oxygenation in brain tumors.