Table 3.
Dynamic contrast-enhanced MRI studies in animal models relevant to dementia.
| Study | Model (species) | Sample Size (Ct/Tg) | Age (months) | DCE Protocol (FS/PS/TA) | CA/Dose (mmol/kg) | VIF | PK Model | Software | Average BBB Ktmns (Ct/Tg; ×10−3 min−1) | Main Findings | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HC | CTX | THAL | CC | |||||||||||
| Pericyte deficiency | Nikolakop oulou et al., 2019 | Pericyte-Cre-DTR (mouse) | 5/6 | 2–3 | 7T/VFA-FLASH/15min | Magnevist (0.5) | CCA | Patlak | Rocketship | 0.59#/1.13# | 0.68#/1.23# | NK | NK | Increased BBB permeability after pericyte ablation |
| Montagne et al., 2018 | PdgfrbF7/F7 (mouse) | 5–7/5–7 | 1–1.5, 3–4, 9–12 | 7T/VTR-FLASH/35min | Magnevist (0.5) | CCA | Patlak | Rocketship | NK | NK | NK | 0.60/0.86, 0.58/1.05, 0.70/1.22 | Increased BBB permeability in pericyte-depleted WM regions | |
| Amyloid models | Dickie et al., 2021 | TgF344-AD (rat) | 16/13, 5/7, 7/8 | 13, 18, 21 | 7T/VFA-SPGR/10min | Dotarem (0.5) | SSS | Patlak | R | NK | NK | NK | NK | AD genotype did not lead to Ktrans changes, but higher water permeability (Kw) was observed |
| Montagne et al., 2021 | 5xFAD; TR-APOE3/4 (mouse) | 12-14 FAD−/13-16 FAD+ | 18–24 | 7T/VFA-FLASH/25min | Gd-DTPA (BioPAL) (0.5) | CCA | Patlak | Rocketship | 0.68/0.98$ | 0.69/0.91$ | NK | NK | Increased BBB permeability in APOE4 AD mice, independent of amyloid pathology | |
| Wang et al., 2018 | SHR (rat) | 5/5 | 17 | 7T/Spin Echo/35min | Magnevist (0.2) | NK | Extended Tofts | DCE@urLAB | 8.40/31.60 | 5.20/30.20 | NK | NK | Increased BBB permeability and Aβ accumulation in HC and CTX of SHR rats | |
| Xu et al., 2017 | Diabetes (rhesus monkey) | 6/5 | 13 years | 3T/SRGRE/10 min | MultiHance (0.1) | SSS | Extended Tofts | DCE@urLAB | 3.32/7.91 | 3.27/8.11 | 3.30/7.47 | NK | Increased BBB permeability in diabetic monkeys | |
Abbreviations: Aβ: Amyloid-beta; AD: Alzheimer’s Disease; APOE4: Apolipoprotein E4; BBB: Blood-Brain Barrier; CA: Contrast Agent; CCA: Common Carotid Artery; cSVD: Cerebral Small Vessel Disease; Ct: Controls; CTX: Cortex; DTR: Diphtheria Toxin Receptor; DT-SRGRE: Dual-time SRGRE; FAD: Familial Alzheimer’s Disease; FLASH: Fast Low Angle Shot; FS: Field Strength; HC: Hippocampus; Ki & Ktrans: Blood-to-Brain Transfer Constant; Kw: Blood-to-Brain Water Exchange Rate; NK: Not Known; Pdgfrb: Platelet-Derived Growth Factor Receptor b; PK: Pharmacokinetic; PS: Pulse Sequence; SHR: Spontaneously Hypertensive Rat; SPGR: Spoiled Gradient; SRGRE: Saturation Recovery Gradient Echo; SSS: Superior Sagittal Sinus; TA: Time Acquisition; Tg: Transgenic Animals; TR: Targeted Replacement; THAL: Thalamus; VFA: Variable Flip Angle; VIF: Vascular Input Function; VTR: Variable Time Repetition.
BBB Ktrans values from 15 days post Diphtheria Toxin treatment;
BBB Ktrans values from TR-APOE4;5xFAD (Tg) vs TR-APOE3;5xFAD (Ct) mice.