Table 3.
Guidelines for design and analysis of pharmacological RSfMRI studies
| Minimum standards | Advanced state‐of‐the‐art | Section in text | |
|---|---|---|---|
| Design Considerations | |||
| Study Objectives | Experimental Objectives and Clinical Relevance | ||
| Pharmacokinetics | 10‐min RSfMRIs, repeated as needed to cover the entire duration of drug administration and washout | Fast RSfMRI | Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling |
| Baselines and Control | Placebo Control | Pre‐drug, post‐washout scans in both drug session and placebo session | Biological Confounds |
| Health condition | Full screening of prescriptions as well as medical screening of physiological and metabolic state | Biological Confounds | |
| Mode of administrations | Single or multi‐dose oral | PK‐controlled infusion | Table 1 |
| MRI Acquisition | |||
| Anatomical | T1W anatomical MRI | TOF‐MRA | Biological Confounds, Standardizing Multivariate Data Acquisition |
| Functional fMRI | T2*w EPI (TR/TE = 2,000/30), 5–10 min | Ultrafast T2* , dual‐echo BOLD/ASL | Pharmacological fMRI (Pharma‐fMRI), Spontaneous BOLD Signal Fluctuations and Functional Networks, Standardizing Multivariate Data Acquisition |
| Blood flow | pCASL | VS‐ASL, TE‐ASL | Arterial Spin Labeling and Cerebral Perfusion |
| Myelination | DWI | Standardizing Multivariate Data Acquisition | |
| Biomarkers | |||
| Functional connectivity | Seed‐based or NOI‐based networks | Dynamic FC, hierarchical clusters | Spontaneous BOLD Signal Fluctuations and Functional Networks and Reliability, Reproducibility |
| ICA | sICA, tICA, gICA | ICASSO, RELICA | Spontaneous BOLD Signal Fluctuations and Functional Networks and Reliability, Reproducibility |
| Graph | Centrality, efficiency, small worldness, path length | Dynamic modularity, assortativity | Spontaneous BOLD Signal Fluctuations and Functional Networks, Dose/Response in Anesthesiology, and Reliability, Reproducibility |
| spatial coherence | REHO | Spontaneous BOLD Signal Fluctuations and Functional Networks, and Reliability, Reproducibility | |
| Spectral features | f(ALFF) | Spontaneous BOLD Signal Fluctuations and Functional Networks, and Reliability, Reproducibility | |
| CBF | Average biophysical model of perfusion weighted images | ATT | Arterial Spin Labeling and Cerebral Perfusion and Combined ASL/BOLD fMRI and Neurovascular Coupling |
| BOLD signal | Fitting a hemodynamic response to drug's pharmacokinetic curve. | Pharmacological fMRI (Pharma‐fMRI), Dose/Response in Anesthesiology, and Methods Validation and Calibration | |
| Preprocessing | |||
| Motion | Realignment to a frame of reference | Scrubbing, including motion regressors, ICA‐based correction | Structured Noise and Artifact Removal and Reliability, Reproducibility |
| Physiological noise | Monitoring and regressing out (e.g., RETROICOR, RVHRCOR) | Post hoc analysis of neurobiological correlates | Biological Confounds and Structured Noise and Artifact Removal |
| Global signal regression | Controversial | Compare results with and without regressors | Structured Noise and Artifact Removal and Reliability, Reproducibility |
| Registration | Functional to anatomical | Biological Confounds | |
| Validity | |||
| Stability | Standardized acquisition and preprocessing | Characterization of non‐stationarity, dynamic connectivity and hierarchical clustering | Reliability, Reproducibility |
| Test‐retest reliability | Different subjects, similar biomarkers | Same subject, same biomarker from repeated measurements | Reliability, Reproducibility |
| Interpretation | Hybrid PET/MRI, hybrid BOLD/CBF, meta‐analysis | Experimental Objectives and Clinical Relevance, Biological Confounds, Data‐Sharing and Meta‐Analysis of the Existing Data, and Contributions From PET | |
| Statistics | |||
| Univariate analysis | Mixed effect multilevel GLM | Multi‐scale adaptive GEE, Sandwich estimator | Statistical Analysis |
| Multivariate analysis | MGLM | Machine learning (SVM, response prediction, GCP dose/response‐prediction) | Statistical Analysis , Data‐Sharing and Meta‐Analysis of the Existing Data |
| Statistical thresholding | FDR, cluster‐correction, TFCE | Permutation testing | Statistical Analysis |
| Covariates of interest | |||
| Structured noise | Anatomical correlates of Physiology and motion | Structured Noise and Artifact Removal | |
| Psychophysical states | Eyes open/close | Anxiety, arousal, physiological rates | Biological Confounds , Structured Noise and Artifact Removal |
| Circadian phases | Control time of day | Collect blood/saliva samples | Biological Confounds |
| Age and sex | Control for variations in age and sex group analysis | Include anatomical MRIs as a covariate in group analysis | Biological Confounds |