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Targeted MRI (tMRI) of Small Changes in the T1 of White Matter of the Brain in Methamphetamine Dependency Before and After Abstinence.
Paul Condron1,2, Gil Newburn1, Eryn Kwon1,2,3, Taylor Emsden1,2, Benjamin Bristow1,2, Maryam Tayebi1,2, Tuta Ngarimu4, Wendy Mohi1, Samantha J Holdsworth1,2, Daniel Cornfeld1,2, Miriam Scadeng1,2, and Graeme M Bydder1,5
1Mātai Medical Research Institute, Gisborne, New Zealand, 2The University of Auckland, Auckland, New Zealand, 3Auckland Bioengineering Institute, Auckland, New Zealand, 4Manaaki Moves, Gisborne, New Zealand, 5University of California San Diego, San Diego, CA, United States

Synopsis

Keywords: Neuroinflammation, Drugs, tMRI, Methamphetamine recovery, WM recovery

Motivation: Targeted MRI (tMRI) of small changes in T1 in lesions in normal appearing white matter using divided Subtracted Inversion Recovery (dSIR) sequences can show high contrast and abnormalities that are not seen with conventional IR sequences.

Goal(s): To depict subtle changes in T1 in otherwise normal appearing white matter with dSIR images.

Approach: Applying tMRI in a patient with methamphetamine dependency before and eight months after abstinence.

Results: Widespread abnormalities on dSIR images in areas of normal appearing WM n T2-FLAIR images. There was striking remission of the changes after eight months' abstinence. The changes may be due to neuroinflammation regression with abstinence.

Impact: In a patient with methamphetamine dependency, tMRI using dSIR sequences showed striking abnormalities in white matter that appeared normal with T2-FLAIR sequences of the brain. These changes showed marked regression after eight months' abstinence.

Background

The commonest finding with clinical MRI of the brain in methamphetamine addiction is white matter hyperintensities which are non-specific and only present in a minority of patients1-3. There is pathological evidence of neuroinflammation in the brain of methamphetamine addicts4. This may cause small increases in T1 and/or T2 in white matter of the brain but conventional sequences may not be sensitive enough to produce recognizable contrast from them. To address this, a divided Subtracted Inversion Recovery (dSIR) sequence was implemented since this sequence can increase the contrast produced by small changes in T1 by ten times5,6 and could therefore reveal abnormalities not apparent with conventional sequences. The mechanism underlying dSIR sequence contrast is shown in Figures 1 and 2.
Two magnitude reconstructed inversion (IR) T1-filters with different TIs (TIshort = TIs and TI intermediate = TIi) are shown in Figure 1A. They are subtracted to give the Subtracted IR (SIR) T1-filter in Figure 1B. This T1-filter is steep in the X axis region between the two nulling TIs of the T1-filters (i.e. TIs and TIi) shown in Figure 1A, i.e., in the middle Domain (mD). The two T1-filters in Figure 1A can also be added as an Added AIR T1-filter which is shown in Figure 1C.Within the mD of the AIR T1-filter there is a low signal.
Figure 2A shows the divided subtracted IR (dSIR) T1-bipolar filter in which the SIR T1-filter in Figure 2B is divided by the AIR T1-filter in Figure 2C. It shows a highly positive nearly linear slope in its mD.
Figure 2B compares the contrast (difference in signal) produced by the STIs T1-filter (pink) which is that of a conventional IR sequence such as MP-RAGE, to the contrast produced by a SIR T1-filter (blue) from the same increase in T1 (horizontal green arrow). The vertical arrows on the right show that the contrast produced by the SIR T1-filter (blue) is double that produced by the STIs T1-filter (pink).
Figure 2C compares the contrast produced by the STIs T1-filter, (pink) to that from the dSIR T1-bipolar filter (blue) from the same increase in T1 (horizontal green arrow). The dSIR T1-bipolar filter generates ten times more contrast (blue arrow on the right) than the STIs T1-filter (pink arrow on right).

Methods

With approval from the New Zealand Health and Disability Ethics Committee (2022 EXP 11360), a 49 y/o male normal control matched for age, gender, ethnicity and socioeconomic status, and a 51 y/o male patient with a long history of methamphetamine dependency were scanned on a 3T scanner (SIGNA Premier; General Electric Healthcare, Milwaukee, WI). 2D dSIR-Fast Spin Echo sequences were performed with a TIs chosen to null normal white matter and a longer TIi chosen to produce narrow mD dSIR images targeted at small increases in T1 from normal in white matter, as illustrated in Figure 2C. Positionally matched T2-wFSE and T2-FLAIR images were acquired for comparison (Table 1). The patient was examined before abstinence and after eight months' abstinence.

Results

Figure 3 (left column) shows narrow mD dSIR images in the normal control. More peripheral normal white matter appears dark and the more central normal white matter of the superior longitudinal fasciculi appears mid-gray with an antero-posterior gradation of increased signal. Figure 3 (right column) shows narrow mD dSIR images from the patient. There are extensive areas of high signal with white matter with only small areas of normal dark white matter (white arrows). Figure 4 compares T2-FLAIR images (left column) with matched narrow mD dSIR images (right column) in the patient. No abnormality is seen in the white matter on the T2-FLAIR images (left column) but extensive high signal abnormalities are seen in white matter on the narrow mD dSIR images. Small areas of normal white matter with a dark appearance are shown by the white arrows (right column). Figure 5 shows narrow mD dSIR images in the patient before abstinence (left column) and after eight months' abstinence (right column). There is extensive reduction in the extent of the high signal abnormalities in white matter on the dSIR images at all three levels consistent with marked disease regression (right column).

Discussion

The most likely cause of the changes in white matter is neuroinflammation induced by methamphetamine and possibly other chemicals associated with its illicit preparation7,8. The regression after abstinence supports neuroinflammation as the dominant pathological process, rather than gliosis or neurodegeneration which may not be reversible. tMRI using dSIR sequences could revolutionize the diagnosis of brain changes in methamphetamine dependency.

Acknowledgements

We would like to acknowledge support from the Fred Lewis Enterprise Foundation, Manaaki Moves Trust, and Kānoa New Zealand. We are also grateful for support from the people of Tairāwhite, GE Healthcare and Mātai Ngā Māngai Māori.

References

1. Bae SC, Lyoo IK, Sung YH, Yoo J, Chung A, Yoon S-J, et al. Increased white matter hyperintensities in male methamphetamine abusers. Drug and Alcohol Dependence 2006;81(1):83-88.

2. Alaee A, Zarghami M, Farnia S, Khodemloo M, Khoddad T. Comparison of brain white matter hyperintensities in methamphetamine and methadone dependent patients and healthy controls. Iran J Radiol 2014;11(2):e14275.

3. Huang S, Yang W, Yan C, Liu J. White matter abnormalities based on TBSS and its correlation with impulsivity behavior of methamphetamine addicts. Front Psychiatry 2020;11:452. doi: 10.3389/fpsyt.2020.00452.

4. Ghavidel N, Khodagholi F, Ahmadiani A, Khosrowabadi R, Asadi S, Shams J. Inflammation but not programmed cell death is activated in methamphetamine-dependent patients: relevance to the brain function. Int J Psycholophysiol 2020;157:42-50.

5. Ma YJ, Moazamian D, Cornfeld DM, Condron P, Holdsworth SJ, Bydder M, Du J, Bydder GM. Improving the understanding and performance of clinical MRI using tissue property filters and the central contrast theorem, MASDIR pulse sequences and synergistic contrast MRI. Quant Imaging Med Surg. 2022;12(9):4658-90.

6. Ma YJ, Moazamian D, Port JD, Edjlali M, Pruvo JP, Hacein-Bey L, et al. Targeted magnetic resonance imaging (tMRI) of small changes in the T1 and spatial properties of normal or near normal appearing white and gray matter in disease of the brain using divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences. Quant Imaging Med Surg 2023;13(10):7304-7337.

7. Quarantelli M. MRI/MRS in neuroinflammation: methodology and applications. Clin Transl Imaging 2015;3:475–489 8. Laule C, Port JD (Eds). Imaging Neuroinflammation. Cambridge MA, Academic Press, 2023.

Figures

Figure 1. Subtracted IR (SIR) and Added IR (AIR) T1-filters. T1 is shown along the linear X axes in ms. (A) shows the TIs T1-filter (pink) and TIi T1-filter (blue), (B) shows the subtraction (STIs - STIi) IR or SIR T1-filter, and (C) shows the addition (STIs + STIi) IR or AIR T1-filter. In (B) the slope of the curve in the mD in the SIR T1-filter is about double that of the STIs filter (pink in [A]). In (C) the signal at T1=0 is doubled to 2.0, and the signal in the mD is reduced to about 0.20 in the nearly linear, slightly downward sloping central part of the AIR T1-filter (i.e. in the middle Domain, mD).

Figure 2. Shows division of the SIR T1-filter (Fig. 1B) by the addition T1-filter (Fig. 1C) to give the dSIR T1-bipolar filter. (2B) shows comparison of the conventional IR STIs T1-filter (pink) and the SIR T1-filter (blue) for a small increase in T1 (green arrow). (2C) is a comparison of the STIs T1-filter (pink) with dSIR T1-filter (blue) for the small increase in T1. In (B) the contrast with the SIR T1-filter is twice that with the IR T1-filter (blue and pink arrows). In (C) the contrast with the dSIR T1-bipolar filter is ten times greater than that of the IR T1-filter (blue and pink arrows).

Figure 3. 2D dSIR narrow mD images in the control (left column) and the patient (right column) are shown. The narrow mD dSIR images on the control show normal white matter as very low signal intensity (dark). The narrow mD dSIR images on the patient show widespread high signal changes in white matter with only small areas of normal dark white matter (arrows). Normal high signal boundaries are seen between white matter and gray matter on the dSIR images in the control and the patient, but are less obvious in the patient because of the high signal in his abnormal white matter.

Figure 4. Patient with methamphetamine dependency. Comparison of T2-FLAIR and narrow mD dSIR images. Little or no abnormality is seen on the T2-FLAIR image (left column) but there are extensive areas of higher signal in about 90% of the white matter of the centrum semiovale (right column). Only small areas of normal low signal are seen in the white matter (arrows) (right).

Figure 5. Patient with methamphetamine dependency. Comparison of narrow mD dSIR images before abstinence and eight months after abstinence. The before abstinence narrow mD dSIR images show widespread abnormal areas of increased signal in white matter (left column). The eight months after abstinence images show marked regression of the abnormalities with extensive dark low signal areas of normal white matter now present (right column).

Table 1. Pulse sequences and pulse sequence parameters used at 3T. Z = zipped

Proc. Intl. Soc. Mag. Reson. Med. 32 (2024)
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DOI: https://doi.org/10.58530/2024/2505