Additional MRI measures of brain in SCD requiring further research as potential end points in clinical trials
| 3 Tesla MRI method . | Outcome measure . | Rationale . | Duration, min . |
|---|---|---|---|
| Head time-of-flight magnetic resonance angiography | 1. Vasculopathy (percent; categorical) | Noninvasive alternative to head CTA/DSA; categorical grading (use 0-4)205 | 5 |
| 2. Associated pathology (eg, moya-moya) | |||
| Neck time-of-flight magnetic resonance angiography | 1. Vasculopathy (percent; categorical) | Noninvasive alternative to neck CTA; presence of cervical vasculopathy extent remains debated in SCD | 6 |
| Diffusion tensor imaging | 1. White matter structural connectivity | Fiber tracking and related parameters (anisotropy, diffusivity) may indicate white matter damage and describe symptomatology | 6 |
| 2. Tract-based spatial statistics | |||
| 3. Fractional anisotropy, mean diffusivity, etc | |||
| Susceptibility weighted imaging | 1. Microbleeds (count; volume) | Characterize microvascular disease and iron deposition | 4 |
| 2. Quantitative susceptibility (iron) | |||
| 3. Venous density | |||
| Diffusion-weighted imaging if acute CNS event | 1. Acute infarct (count) | Inform presence of recent infarcts | 1 |
| MR venography if acute CNS event | Thrombosis, stenosis | Unlikely to be abnormal in asymptomatic | |
| Hemometabolic | |||
| Arterial spin labeling | 1. Regional cerebral blood flow (mL/100g/min) | Inform extent of hypo- or hyperperfusion; hypoperfusion indicative of tissue-level impairment from vasculopathy; hyperperfusion marker of how well parenchyma is responding to anemia and reduced blood delivery; may also provide indicator of arterial-venous shunting | 4 |
| T2-relaxation-under-spin-tagging | 1. OEF (ratio of oxygen consumed to oxygen delivered) | Inform extent to which total oxygen delivery is meeting requirements; elevated OEF may be indicator of new or recurrent infarct; reduced CMRO2 may indicate suppressed neuronal activity and new lesion risk | 2 |
| 2. CMRO2; mL O2/100 g/min; requires CBF measurement | |||
| Phase contrast angiography (head and neck) | 1. Quantitative velocity assessment of major intracranial (eg, first segment MCA) and cervical vessels (ICA, BA) (mm/s) | Allows for whole-brain CBF assessment (with tissue volume information), which is not possible with arterial spin labeling; evaluate elevated flow velocity (provide comparison for TCD) | |
| Blood oxygenation level-dependent or arterial spin labeling cerebrovascular reactivity (requires respiratory stimulus such as hypercapnic or IV/oral vasodilatory stimulus such as acetazolamide) | 1. Cerebrovascular reactivity, an indicator of microvascular reserve capacity (signal change) | Cerebrovascular reserve will be exhausted when CBF can no longer increase to compensate for anemia and/or vasculopathy | 8 |
| 3 Tesla MRI method . | Outcome measure . | Rationale . | Duration, min . |
|---|---|---|---|
| Head time-of-flight magnetic resonance angiography | 1. Vasculopathy (percent; categorical) | Noninvasive alternative to head CTA/DSA; categorical grading (use 0-4)205 | 5 |
| 2. Associated pathology (eg, moya-moya) | |||
| Neck time-of-flight magnetic resonance angiography | 1. Vasculopathy (percent; categorical) | Noninvasive alternative to neck CTA; presence of cervical vasculopathy extent remains debated in SCD | 6 |
| Diffusion tensor imaging | 1. White matter structural connectivity | Fiber tracking and related parameters (anisotropy, diffusivity) may indicate white matter damage and describe symptomatology | 6 |
| 2. Tract-based spatial statistics | |||
| 3. Fractional anisotropy, mean diffusivity, etc | |||
| Susceptibility weighted imaging | 1. Microbleeds (count; volume) | Characterize microvascular disease and iron deposition | 4 |
| 2. Quantitative susceptibility (iron) | |||
| 3. Venous density | |||
| Diffusion-weighted imaging if acute CNS event | 1. Acute infarct (count) | Inform presence of recent infarcts | 1 |
| MR venography if acute CNS event | Thrombosis, stenosis | Unlikely to be abnormal in asymptomatic | |
| Hemometabolic | |||
| Arterial spin labeling | 1. Regional cerebral blood flow (mL/100g/min) | Inform extent of hypo- or hyperperfusion; hypoperfusion indicative of tissue-level impairment from vasculopathy; hyperperfusion marker of how well parenchyma is responding to anemia and reduced blood delivery; may also provide indicator of arterial-venous shunting | 4 |
| T2-relaxation-under-spin-tagging | 1. OEF (ratio of oxygen consumed to oxygen delivered) | Inform extent to which total oxygen delivery is meeting requirements; elevated OEF may be indicator of new or recurrent infarct; reduced CMRO2 may indicate suppressed neuronal activity and new lesion risk | 2 |
| 2. CMRO2; mL O2/100 g/min; requires CBF measurement | |||
| Phase contrast angiography (head and neck) | 1. Quantitative velocity assessment of major intracranial (eg, first segment MCA) and cervical vessels (ICA, BA) (mm/s) | Allows for whole-brain CBF assessment (with tissue volume information), which is not possible with arterial spin labeling; evaluate elevated flow velocity (provide comparison for TCD) | |
| Blood oxygenation level-dependent or arterial spin labeling cerebrovascular reactivity (requires respiratory stimulus such as hypercapnic or IV/oral vasodilatory stimulus such as acetazolamide) | 1. Cerebrovascular reactivity, an indicator of microvascular reserve capacity (signal change) | Cerebrovascular reserve will be exhausted when CBF can no longer increase to compensate for anemia and/or vasculopathy | 8 |
An adjudication committee is strongly recommended for imaging outcomes. Vasculopathy is a surrogate marker and difficult to measure as an outcome.
BA, basilar artery; CBF, cerebral blood flow; CMRO2, cerebral metabolic rate of O2 consumption; CTA, computed tomographic angiography; DSA, digital subtraction angiography; MR, magnetic resonance; OEF, oxygen extraction fraction.