5088

Modeling and selection of T1 and T2 tissue mimics for 0.0065T, 0.064T, 0.55T MRI using agarose with manganese, gadolinium, copper, or nickel
Kalina V Jordanova1, Ye Tian2, Sheng Shen3, Michele N Martin1, Megan E Poorman4, Rui Pedro Teixeira4, Krishna S Nayak2, Matthew S Rosen3,5, and Kathryn E Keenan1
1NIST: National Institute of Standards and Technology, Boulder, CO, United States, 2Ming Hsieh Department of Electrical and Computer Engineering, University of Southern California, Los Angeles, CA, United States, 3Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States, 4Hyperfine, Inc., Guilford, CT, United States, 5Department of Physics, Harvard University, Cambridge, MA, United States

Synopsis

Keywords: Quantitative Imaging, Relaxometry

There is re-emerging interest in MRI fields ≤0.55T as well as quantitative MRI (qMRI) methods. Physiologically relevant reference objects are needed to adapt qMRI techniques to lower fields.

We investigate materials as tissue mimics for brain imaging at 0.0065T, 0.064T, 0.55T, for white matter, gray matter, fat, cerebrospinal fluid, and blood. We create samples composed of agarose and paramagnetic salts and measure relaxation across field strengths. Samples suitable to mimic each tissue are presented for each field strength. This work will facilitate qMRI development for fields ≤0.55T by providing accessible mimic compositions to the community.

Introduction

There is re-emerging interest in MRI fields ≤0.55T as alternatives to conventional MRI (1.5-7T) due to lower cost and greater accessibility1. Quantitative MRI (qMRI) methods are increasingly used to differentiate tissue2 and have promising clinical utility3,4. Tissue properties may vary with field strength, necessitating physiologically relevant reference objects to adapt qMRI techniques to diverse fields1,5.

We investigate materials as tissue mimics for brain imaging at 0.0065T, 0.064T, 0.55T, using literature reviews to extrapolate target tissue T1 and T2 for white matter (WM), gray matter (GM), fat, cerebrospinal fluid (CSF), and blood. We create samples composed of agarose and paramagnetic salts and measure relaxation across field strengths. From these results we suggest mimic compositions for each tissue and field. This work will facilitate qMRI development for fields ≤0.55T by providing accessible mimic compositions to the community.

Methods

Data Acquisition
Target T1 and T2 values for each tissue (WM, GM, CSF, fat, blood) were extrapolated from literature measurements from a variety of similar field strengths (data not shown)6-26.

Chemical samples were prepared by dissolving stock solutions of metal compounds (CuSO4·5H2027, GdCl3·6H2028-EDTA29, MnCl2·4H2030, NiCl2·6H2031) into distilled water. GdCl3-EDTA was made by stirring a GdCl3 and EDTA solution on a 98C hotplate for 30 minutes. Dry agarose32 was weighed and added to the paramagnetic salt solution, followed by heat cycles: (1) 30s interval microwave cycle until boiling; (2) 10-minute hotplate cycle to ensure well-hydrated agarose. Distilled water was added to the mixture to account for evaporation. The mixture was poured into 50ml, 30ml, or 2ml tubes, pre-washed with isopropyl alcohol.

The primary systems used to measure T1 and T2 for each field strength were: 0.0065T33,34; 0.064T (Hyperfine Swoop, hardware 1.8, software rc8.5.0); 0.55T (Siemens, prototype MAGNETOM Aera XQ). Supplemental measurements were acquired at 0.0065T and 0.55T using variable field NMR systems (Tecmag Redstone, TNMR software).

T1 was measured using inversion recovery protocols; T2 was measured using spin echo or Carr-Purcell-Meiboom-Gill (CPMG) sequences (see details in Figure 1). T1 was calculated using:
$$S_i=S_0(1-(1+d)e^{-TI/T1}+e^{-TR/T1})) \qquad (1)$$
with T1 the target value to fit, inversion time TI, repetition time TR, scale factor for imperfect inversion d, nominal signal intensity $$$S_0$$$, and measured signal intensity $$$S_i$$$. Similarly, T2 was calculated using:
$$S_i=S_0e^{-TE/T2} \qquad (2)$$
with T2 the target value to fit, and echo time TE.

Tissue Mimic Sample Selection
For each paramagnetic salt and field, a model was fit35,36 relating T1 and T2 to paramagnetic salt (N) and agarose (A) concentrations:
$$\frac{1}{T_1}=a_1+a_2A+a_3A^2+a_4N+a_5N^2+a_6AN+a_7A^2N+a_8AN^2+a_9A^2N^2 \qquad (3)$$
$$\frac{1}{T_2}=b_1+b_2A+b_3A^2+b_4N+b_5N^2+b_6AN+b_7A^2N+b_8AN^2+b_9A^2N^2 \qquad (4)$$
An agarose-only model limited to the first three terms of Eq 3-4 was fit to establish values for coefficients {a,b}1-3. A metal-only model was fit to establish {a,b}1,4-5. The average from the two fits for {a,b}1 is used. These coefficients {a,b}1-5 were fixed when modeling Eq 3-4 with all terms. Each fitting used Python’s lmfit package. Coefficients were constrained as ≥0, and small coefficients of magnitude ≤1e-4 were zeroed (no appreciable effect was observed in the fit).

To calculate sample concentrations for each target tissue mimic, Python sympy was used to solve the inverse of Eq 3-4 for each target value and field. For targets lying entirely outside the sample space, mimics for T1 and T2 were calculated individually.

Results

Figures 2-5(a-c) show sample T1 and T2 measurements for each field, for each paramagnetic salt and agarose combination. Additionally, the fits to Eq 3-4 are plotted as lines indicating constant agarose or constant salt. Target tissue T1 and T2 are plotted for each field (open circles), and sample mimics selected for each tissue are shown (small closed circles).

Tables in Figures 2-5(d) indicate each tissue mimic’s salt and agarose concentrations for each field.

Discussion and Conclusion

Suitable tissue mimics were selected for 0.0065T, 0.064T, and 0.55T, for blood, fat, CSF, WM, and GM (Figures 2-5(d)). Most tissues have a suitable mimic for each chemical composition and field.

Some tissues lie outside of the T1-T2 sample space; CSF always falls into this category. This is expected, as the body temperature of 37C leads to elevated T1, which can be difficult or even impossible to mimic at the typically much-lower laboratory temperature of phantom samples. Although lab temperature distilled water has a lower T1 than CSF, it may be the best mimic for all field strengths, since most of the modeled mimics use very small amounts of agarose that may be difficult to manufacture. Additionally, fat is difficult to mimic using the MnCl2 mixtures due to reduced T2 of the samples; therefore, samples mimicking either T1 or T2 of fat using MnCl2 were provided.

T1 and T2 models as a function of paramagnetic salt and agarose concentrations were created using Eq 3-4. These are purely empirical models, and improvements can be made by including relaxation physics.

By providing multiple mimics for the same target tissue at each field strength, we aim to increase accessibility to accurate phantom materials, encouraging more studies and ultimately clinical utility for qMRI.

Acknowledgements

MSR acknowledges the gracious support of the Kiyomi and Ed Baird MGH Research Scholar Award. This work was supported in part by 1R21CA267315-01A1 (PIs Rosen and Keenan).

NIST acknowledges research funding from the National Research Council Postdoctoral Fellowship.

The USC authors acknowledge grant support from the National Science Foundation and National Institutes of Health, and research support from Siemens Healthineers.

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Figures

Figure 1: T1 and T2 scan parameters for each system. When multiple parameter values are given the chosen parameters were dependent on the expected T1 and T2 of the sample.

Figure 2: a-c) T1 and T2 measurements for CuSO4 + agarose samples for (a) 0.0065T, (b) 0.064T, (c) 0.55T. Sample models (Eq 3-4) are displayed via constant agarose concentration lines (solid) and constant CuSO4 concentration lines (dashed). Target tissue mimics (closed circles) are given for each tissue target (open circles; Blood=red, CSF=maroon, Fat=blue, GM=black, WM=gray). d) Table giving target tissue T1 and T2, and the CuSO4 and agarose concentrations that result in a mimic for each field strength, as well as the expected sample T1 and T2 from Eq 3-4.

Figure 3: a-c) T1 and T2 measurements for GdCl3-EDTA + agarose samples for (a) 0.0065T, (b) 0.064T, (c) 0.55T. Sample models (Eq 3-4) are displayed via constant agarose concentration lines (solid) and constant GdCl3-EDTA concentration lines (dashed). Target tissue mimics (closed circles) are given for each tissue target (open circles; Blood=red, CSF=maroon, Fat=blue, GM=black, WM=gray). d) Table giving target tissue T1 and T2, and the GdCl3-EDTA and agarose concentrations that result in a mimic for each field strength, as well as the expected sample T1 and T2 from Eq 3-4.

Figure 4: a-c) T1 and T2 measurements for MnCl2 + agarose samples for (a) 0.0065T, (b) 0.064T, (c) 0.55T. Sample models (Eq 3-4) are displayed via constant agarose concentration lines (solid) and constant MnCl2 concentration lines (dashed). Target tissue mimics (closed circles) are given for each tissue target (open circles; Blood=red, CSF=maroon, Fat=blue, GM=black, WM=gray). d) Table giving target tissue T1 and T2, and the MnCl2 and agarose concentrations that result in a mimic for each field strength, as well as the expected sample T1 and T2 from Eq 3-4.

Figure 5: a-c) T1 and T2 measurements for NiCl2 + agarose samples for (a) 0.0065T, (b) 0.064T, (c) 0.55T. Sample models (Eq 3-4) are displayed via constant agarose concentration lines (solid) and constant NiCl2 concentration lines (dashed). Target tissue mimics (closed circles) are given for each tissue target (open circles; Blood=red, CSF=maroon, Fat=blue, GM=black, WM=gray). d) Table giving target tissue T1 and T2, and the NiCl2 and agarose concentrations that result in a mimic for each field strength, as well as the expected sample T1 and T2 from Eq 3-4.

Proc. Intl. Soc. Mag. Reson. Med. 31 (2023)
5088
DOI: https://doi.org/10.58530/2023/5088