Advanced Functional and Structural MRI Techniques for Neuropharmacological Imaging

Objective:

Functional and structural magnetic resonance imaging techniques have proven essential for noninvasive mapping of brain physiology and pathology. The primary objective of this protocol is to develop advanced magnetic resonance imaging and spectroscopy (MRI and MRS) techniques for neuroimaging studies related to addiction. These neuroimaging techniques will be used in other studies to better understand the underlying mechanism of drug addiction and to potentially develop strategies for more effective treatment.

Study population:

Healthy controls and drug users will participate in the study. Technical developments of MRI/MRS will be performed on healthy controls, while the evaluation of the applicability of these techniques to addiction related neuroimaging studies will be performed using drug users and healthy controls.

Design:

Based on the fundamental principle of the biophysical transduction of physiological signals to magnetic resonance (MR) imaging and spectroscopic signals, advanced techniques will be developed to measure the activity, metabolism, structure, and biochemistry of the brain. The development of these techniques typically includes the following steps: 1) proof-of-concept computer simulations, 2) implementation of the imaging concept with an MRI scanner and phantoms, 3) feasibility testing on control subjects, and 4) evaluation of the sensitivity and specificity of these techniques in detecting functional changes modulated by task performance, CO2 (5%)administration, or non-invasive neuromodulation techniques (e.g.: transcranial magnetic stimulation (TMS), and transcranial rotating permanent magnet stimulation (TRPMS), 5) evaluation of these techniques in detecting functional and/or structural alterations of the brain related to a specific disease.

Outcome measures:

Advanced neuroimaging techniques developed from this protocol will demonstrate the ability to distinguish between drug using and control populations. Successful techniques will then be incorporated into hypothesis driven studies in the Neuroimaging Research Branch at NIDA-IRP. These techniques will also be useful, through publications and technology transfer, to the entire neuroimaging society.

• Subjects must be between the ages of 18-80, be generally healthy and male or non-pregnant female. Smokers, non-smokers, drug using and non-drug using populations will participate in this study.

Inclusion criteria

General:

• Male and non-pregnant female adults between the ages of 18-80.
• All subjects must be able to provide informed consent.

Exclusion criteria

Subjects will be excluded if they:

• Are pregnant. Urine pregnancy tests will be performed on all female volunteers of child-bearing potential before each experimental session.
• Are unable to undergo MRI scanning due to implanted metallic devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts including Copper 7 IUD) or claustrophobia.
• Have major medical illnesses severe enough to impact data being gathered. Potential exclusions may include a history of chronic uncontrolled hypertension, diabetes, HIV, or other clinically significant medical conditions that may alter the signal being measured.
• Have current major psychiatric disorders to include, but not limited to, mood, anxiety, psychotic disorders.
• Have neurological illnesses severe enough to impact data being gathered. Potential exclusions may include seizure disorders, migraine, multiple sclerosis, movement disorders, or history of significant head trauma, CVA, or CNS tumor. The MAI will assess the severity in relation to the potential impact on data.
• Are non-English speaking. Justification: There is no direct benefit to participants in this study, and some of the study procedures involve more than minimal risk. To include non-English speakers, we would have to translate the consent and other study documents and hire and train bilingual staff, which would require resources that we do not have and could not justify given the small sample size for each experiment. Additionally, the data integrity of some of the cognitive tasks and standardized questionnaires used in this study would be compromised as they have only been validated in English. Most importantly, ongoing communication regarding safety procedures is necessary when participants are undergoing MRI and TMS/TRPMS procedures. The inability to effectively communicate MRI and TMS/TRPMS safety procedures could compromise the safety of non-English speaking participants.
• Are cognitively impaired, as assessed by medical history. A validated IQ test such as the WASI or Shipley-2 may also be considered. Justification: Cognitive impairment and learning disabilities are associated with alterations in brain regions used to accomplish tasks, and, therefore, may introduce significant variably into the data. Cognitive impairment may affect one s ability to give informed consent.

Subjects to be considered for Non-Invasive Brain Stimulation (NIBS) will also be excluded if they:

-Are unable to safely undergo a NIBS procedure as assessed by a TMS safety screening form.

Additional information will be gathered during screening for some experiments. As the purpose of this protocol is to develop imaging techniques, this information will be gathered as needed, depending on the phase of development and specific technique requirements. Based on the scientific and medical requirements of the particular experiment, participants may also be assessed for:

• Age (some experiments may want to target a particular age range. For example, cognitive tasks generally exclude participants over 60, an age when cognitive issues tend to become more commonplace)
• Left-handedness (if desired for a particular task)
• Color-blindness (if using a task requiring color discrimination)
• Drug use diagnosis
• Use of psychoactive or vascularly active medications (if a functional fMRI technique that is sensitive to hemodynamic changes is being used). MAI discretion regarding timeframe of allowed use will be based on clinically relevant factors including drug half-life, pharmacology of the drug in question and pattern of use by the participant.