Echo-Planar Imaging

All MR experiments were performed at room temperature on a 9.4T/31-cm magnet (Magnex, UK), interfaced to a Unity INOVA console (Varian). The actively shielded 12-cm-diameter gradient insert (Magnex, UK) operates at a maximum gradient strength of 40 gauss/cm and a rise time of 120 μs. A 3.8-cm-diameter volume coil (Rapid Biomedical, Ohio) was used for excitation and reception. Metabolite solution (see below) was transferred into a 9-mm I.D. syringe, and three or four syringes were inserted together into the coil for imaging. Magnetic field homogeneity was optimized by localized shimming over a ∼20 × 20 × 6 mm³ volume to yield a water spectral linewidth that was typically 10 Hz or less. The imaging parameters were: a field of view = 24 mm × 24 mm, matrix size = 64 × 64, and slice thickness = 5 mm. Before the SL and CEST experiments, a T₁ map was obtained using an inversion-recovery sequence. In addition, the B₁ field was also mapped for calibration of the transmit power (25 ). With our volume coil, the B₁ map showed fairly good spatial homogeneity: the variation of B₁ was less than 10% across all pixels within the samples (data not shown).
For SL and CEST experiments, the chemical exchange contrast was first generated by the SL or CEST preparation (Fig. 1A); then the residue magnetizations in the X-Y plane were dephased with crushing gradients; and finally, images were acquired with a spin-echo echo-planar imaging (EPI) technique using an echo time (TE) of 42 ms. For on-resonance R_1ρ dispersion experiments, SL was either achieved with the sequence shown in Fig. 1A for Ω = 0 or with an adiabatic SL pulse sequence (25 ); the results were highly similar and are not distinguished here. R_1ρ dispersion was measured for 10 ω_{1, SL} values of approximately 1110, 1570, 2220, 3140, 4440, 6280, 8880, 12560, 17760, and 25120 rad/s. At each ω_{1, SL}, 14 TSL values, ranging between 0 and 330 ms, were acquired with a repetition time (TR) of 8 s and a TE of 42 ms. For CEST and SL Z-spectra measurements, images were collected within ±10 ppm of the water resonance, with the Rabi frequency of a 4-s SL or CEST saturation pulse (ω_{1, SL} or ω_{1, CEST}) = ∼1100 rad/s, and the repetition time was 18 s. At each offset frequency, the SL flip angle θ was adjusted according to θ = arctan(ω_1,SL / Ω). For the calculation of SLR and MTR, control M₀ images were acquired at the offset frequencies of ±300 ppm.
Three sets of MRI phantom experiments were performed:

The cross-sectional nature of the majority of studies examining adolescent neurocognitive functioning makes it difficult to determine the influence of alcohol and drug use on adolescent neurocognition. Therefore, ongoing longitudinal neuroimaging studies are essential to ascertain the degree to which substance intake is linked temporally to adverse changes on indices of brain integrity, or whether neural abnormalities reflect pre-existing patterns. In cross-sectional or longitudinal work, several methodological features are critical to evaluate the potential influence of adolescent substance use on neurocognition. These issues pertain to ensuring participant compliance, accurately assessing potential confounds, and maximizing participant follow-up.
Adolescent compliance as a research participant can be maximized by attending to rapport, building trust, and ensuring privacy of self-report data to the extent that is ethical and feasible to the setting. For behavioral tasks within or outside of imaging, it is critical to ensure participants comprehend task instructions, are fully trained on fMRI tasks, and then are given reminders just prior to task administration. Motion during scan acquisition is detrimental to the quality of imaging data, and is often worse in younger adolescents than older teens or adults. Adolescent head motion can be minimized by the following steps: discuss the importance and rationale for keeping the head still multiple times before and at the scan appointment; model and practice how to say “yes” and “no” when communicating with the research subject from the scanner; model and practice techniques for relaxing and ensuring subjects are in a position suitable for long-term comfort (e.g., legs are not crossed) before scanning begins; maximize participant comfort by using soft cushions around the head and under the knees; and many studies, especially those with younger participants, find practicing scanning in a less expensive mock scanner results in improved participant comfort and more reliable data during data acquisition.
Accurately measuring and accounting for confounds frequently present in adolescent substance-using populations is essential for elucidating the true effect of substance use on adolescent neurocognitive functioning. Common confounds in this population include head injury, depression, ADHD, conduct disorder, prenatal exposure to neurotoxins, family history-related effects, and polysubstance involvement. Conversely, excluding subjects for the aforementioned confounds may impede the generalizability of results. The tradeoff between minimizing confounds and having meaningful, ecologically valid results is an important study design decision, especially given the high cost of fMRI sessions.
Accurately measuring abstinence is another important consideration in substance-related research protocols. If abstinence is required for participation (and compensation) in a study, the dynamics of self-report could change. While biological data may help confirm self-report, these measures are imperfect and do not pinpoint the quantity of specific timing of substance intake 65 (link), 66 . Regarding abstinence from cannabis, obtaining serial quantitative THC metabolite levels, normalized to creatinine, is the best approach for guarding against new use episodes 67 .
Tracking participants over time is a critical part of many clinical issues when interested in the degree to which a variable (e.g., alcohol or marijuana use) might result in neural changes. Although some statistical approaches can help manage attrition, effective tracking procedures are more desirable to ensure study integrity. To maximize participant follow-up, frequent contact with participants must be maintained 68 . Having a well-trained, friendly staff experienced with the population also helps retain participants and parents, and ensures that all participants fully understand the tasks and expectations during the study. Collecting comprehensive contact information can help track adolescents over time in case they should relocate. Additionally, follow-up measures and procedures should be as similar as possible to baseline, except to mitigate learning and practice effects 69 (link). For imaging studies, field map unwarping of EPIs (e.g., fMRI and DTI) should also be considered, as this technique appears to produce more consistent localization of activations 70 (link). Finally, as technical problems are common, back up plans for each piece of equipment used in the neuroimaging session should be in place.