T2* and T1 assessment of abdominal tissue response to graded hypoxia and hypercapnia using a controlled gas mixing circuit for small animals
Tameshwar Ganesh1,2, Marvin Estrada3, James Duffin4, and Hai-Ling Margaret Cheng1,2,5,6

1Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada, 2Physiology & Experimental Medicine, Hospital for Sick Children Research Institute, Toronto, ON, Canada, 3Lab Animal Services, Hospital for Sick Children, Toronto, ON, Canada, 4Anesthesia, University of Toronto, Toronto, ON, Canada, 5Institute of Biomaterials & Biomedical Engineering, University of Toronto, Toronto, ON, Canada, 6The Edward S. Rogers Sr. Department of Electrical & Computer Engineering, University of Toronto, Toronto, ON, Canada

Synopsis

Inspiring gases with altered O2 and CO2 levels is an approach to assess the health of the cerebral vasculature. However, application of this technique in the body is new and less well understood compared to its application in the brain. In this study, we adopt a comprehensive approach to investigate the MR signatures of abdominal tissue response to a wide spectrum of gas challenges. Results in the liver, kidney, and muscle of healthy rats confirmed T2* as a robust marker of blood oxygen saturation but suggested that T1, other than its conventional association to tissue oxygenation, may a marker of blood volume changes.

TARGET AUDIENCE

Physiologists, radiologists, oncologists

PURPOSE

The integration of MR imaging and a gas challenge stimulus (i.e. application of inspired gases containing different levels of O2 and CO2) is a method for non-invasively assessing cerebral vascular response in both health and disease. The application of this approach to assess extra-cranial tissue is an emerging research topic1-3 but is much less thoroughly characterized and understood, especially in the hypoxic regime. In this study, we adopt a comprehensive approach to systematically study and characterize the MRI responses of various extra-cranial tissues to graded levels of hyperoxia, hypercapnia, and hypoxia, using a dedicated gas-mixing circuit for controlled delivery to healthy rats.

METHODS

This study was approved by our institutional animal care committee. A system consisting of a computer-controlled gas mixer, an MR-compatible isoflurane vaporizer, and an MR-compatible ventilator was built to control the delivery of precise levels of gases to small animals. Twelve female adult Sprague Dawley rats (Charles River Laboratories) weighing 250-300 g were anesthetized on 5% isoflurane, intubated with a 14-gauge angiocatheter, and transferred to a water blanket maintained at 38°C. The endotracheal tube was connected to the gas delivery system, and sensors of a mouse oximeter were clipped to the hindpaw to monitor heart rate and blood oxygen saturation. The animal was maintained on 2% isoflurane for the rest of the experiment, resting supine inside an 8-channel wrist coil and imaged on a 3-Tesla scanner (Achieva 3.0 T TX, Philips Medical Systems). Baseline coronal 3D T1-weighted spoiled-gradient echo images with fat suppression were acquired: TR=3.73 ms, TE=1.85 ms, FA=20°, NSA=3, FOV=100mm, ten 3-mm slices, 0.7x0.7 mm in-plane. After 20 minutes of baseline normoxia (21% O2), gas challenges of 10 minute duration were applied, interleaved with 20 minutes of normoxia to return to baseline, during which time ventilation was increased to 104 breaths per minute to wash out residual CO2. Four different types of gas challenge were studied: graded hyperoxia, hypercapnia, hypoxia, and hypercapnic hypoxia. Four animals were used to study each level of gas stimulus. Toward the end of the gas challenge, T1 mapping was performed using a variable flip angle approach 4: FA=2, 10, 20°, TR=5 ms, TE=1.85 ms, NSA=3. T2* mapping was performed using a gradient-echo sequence: TR=50ms, TE=2ms, 32 echoes with 1.485ms spacing, FA=30°, NSA=2. MRI data was analyzed using in-house software in Matlab (v.8.3). Regions of interest were outlined on the liver, kidney cortex, and paraspinal muscle to obtain mean T1 and T2* values. Changes in relaxation times from baseline were compared across animals using two-way ANOVA and post-hoc Tukey-Kramer tests performed at the 95% confidence level.

RESULTS

Fig 1 shows anatomical images and T1 and T2* maps of the liver and kidney in an animal subjected to hypercapnic hypoxia (other gas stimuli not shown). Figs 2 and 3 compare relative changes in T2* and T1 in different abdominal tissues across all animals for all gas challenge levels. As seen in Fig 2, T2* decreased consistently for all hypercapnic and hypoxic challenges, consistent with measured decreases in blood oxygen saturation levels (27% to 45%). T1 decreased on hyperoxia, consistent with increased tissue oxygenation, but decreased also for hypercapnic and hypoxic challenges. As expected, the heart rate lowered (6% to 16%) on hyperoxia and increased (13% to 60%) on many of the hypercapnic and hypoxic challenges.

DISCUSSION

T2* is a sensitive marker of blood oxygen saturation, to the extent that concurrent physiological responses can be potentially masked. T1 is sensitive to tissue oxygenation only under hyperoxia; for hypercapnic and hypoxic challenges, T1 changes are not consistent with changes in tissue oxygenation, suggesting the role of T1 as a weak marker of blood volume.

CONCLUSION

T2* and T1 have complementary roles in evaluating extra-cranial tissue response to a broad range of gas challenges.

Acknowledgements

Funding from the Heart & Stroke Foundation of Canada and the Natural Sciences and Engineering Research Council of Canada.

References

1. Winter JD et al. Normal tissue quantitative T1 and T2* MRI relaxation time responses to hypercapnic and hyperoxic gases. Acad Radiol 2011; 18(9);1159-1167.

2. O’Connor JP et al. Organ-specific effects of oxygen and carbogen gas inhalation on tissue longitudinal relaxation times. Magn Reson Med 2007; 58(3):490-496.

3. Pohlmann A et al. Detailing the relation between renal T2* and renal tissue pO2 using an integrated approach of parametric magnetic resonance imaging and invasive physiological measurements. Invest Radiol 2014;49(8):547-560.

4. Cheng HL and Wright GA. Rapid high-resolution T(1) mapping by variable flip angles: accurate and precise measurements in the presence of radiofrequency field inhomogeneity. Magn Reson Med 2006; 55(3):566-574.

Figures

Fig 1. Hypercapnic hypoxia. The kidney (A-C) and liver (D-F) are shown in a representative animal subjected to 30% CO2 in 12% O2. The kidney is shown on a T1-weighted spoiled-gradient echo image (A) along with pixel-wise T1 maps (B) and T2* maps (C) measured pre- and post-challenge. The liver is shown on a T1-weighted spoiled-gradient echo image (D) along with pixel-wise T1 maps (E) and T2* maps (F) measured pre- and post-challenge.

Fig 2. Changes in T2* relaxation times for different gas challenge regimes. Mean T2* averaged across all animals (N = 4) and standard error are shown for all graded gas challenges in the liver, kidney cortex, and paraspinal muscle. Exceptions are 5% CO2 and 15% CO2 in 12% O2, where only one animal was studied for each. Significant differences from baseline normoxia are indicated (* P < 0.05).

Fig 3. Changes in T1 relaxation times for different gas challenge regimes. Mean T1 averaged across all animals (N = 4) and standard error are shown for all graded gas challenges in the liver, kidney cortex, and paraspinal muscle. Exceptions are 5% CO2 and 15% CO2 in 12% O2, where only one animal was studied for each. Significant differences from baseline normoxia are indicated (* P < 0.05).



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
3929