Brain Morphometry and Longitudinal Relaxation Time of Spontaneously Hypertensive Rats (SHRs) in Early and Intermediate Stages of Hypertension Investigated by 3D VFA-SPGR MRI

Abstract

Cerebral small vessel disease(s) (SVD) result from pathological changes of the small blood vessels in the brain and is common in older people. The diagnostic features by which SVD manifests in brain includes white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and atrophy. In the present study, we use in vivo MRI to characterize brain morphometry and longitudinal relaxation time (T1) of spontaneously hypertensive rats (SHR) to study the contribution of chronic hypertension to SVD relevant pathology. Male SHR and Wistar-Kyoto (WKY) rats underwent 3D variable flip angle spoiled gradient echo brain MRI at 9.4T at early (7 weeks old) and established (19 weeks old) stages of hypertension. The derived proton density weighted and T1 images were utilized for morphometry and to characterize T1 properties in grey matter, white matter (WM) and cerebrospinal fluid (CSF). Custom tissue probability maps were constructed for accurate computerized whole brain tissue segmentations and voxel-wise analyses. Characteristic morphological differences between the two strains included enlarged ventricles, smaller corpus callosum (CC) volumes and general 'thinning' of CC in SHR compared to WKY rats at both age groups. While we did not observe parenchymal T1 differences, the T1 of CSF was

Optimal Mass Transport with Lagrangian Workflow Reveals Advective and Diffusion Driven Solute Transport in the Glymphatic System

“…Another reason that we used the SHRSP rat is that they do not have hydrocephalus -a drawback inherent to other rat strains with chronic hypertension (e.g. SHR rat 56 ) which may affect CSF flow dynamics 7 . The rOMT analysis of DCE-MRI data from the brain showed that the total flux of moving solutes in all tissue compartments (including CSF) was reduced in SHRSP when compared to normotensive WKY rats.…”

“…To study tissue compartment specific glymphatic transport, WKY (N = 7, 8-months old) and SHRSP (N = 7, 8-months old) rats were scanned using the 3D VFA-SPGR sequence (TR/TE/FA/number of averages = 15 ms/4 ms/5~30°/2 scanning time = 30 min 0.30 × 0.30 × 0.30 mm 3 ) as described previously 4,56 . Proton density weighted images calculated from VFA-SPGR were segmented using a custom made SHRSP-WKY rat brain template in deriving spatial registration parameters 4 .…”

Glymphatic Optimal Mass Transport with Lagrangian Workflow Reveals Advective and Diffusion Driven Solute Transport

“…Voxel-based morphometric segmentation of each brain into CSF, grey matter (GM) and white matter (WM) tissue masks derived from anatomical proton-weighted MRIs of the two rat strains (see methods) were used to calculate influx and efflux rate constants as well as tracer distribution volumes across brain compartments. A known feature of the spontaneously hypertensive rat (SHR) strain used in previous GS studies 37,40 is innate hydrocephalus 41,42 , which can affect CSF fluid dynamics long-term 43 . However, no major morphometric differences were observed between WKY and SHRSP rats, and hydrocephalus was not present in SHRSP rats ( Supplementary Fig.…”

“…To study anatomical volumetric differences between WKY and SHRSP rats, we implemented deformation-based morphometry as reported previously 41 . For this purpose, WKY (N=7, 8-months old) and SHRSP (N=6, 8-months old) were scanned using 3D spoiled gradient echo (SPGR) sequence with the following parameters: (TR/TE/FA/Ave = 50ms/4ms/7°/4 scanning time= 23min field of view (30x30x15 mm) reconstructed at isotropic spatial resolution of 0.23x0.23x0.23 mm.…”

“…To study tissue compartment specific glymphatic transport, WKY (N=7, 8-months old) and SHRSP (N=7, 8-months old) were scanned using the 3D VFA-SPGR sequence (TR/TE/FA/Ave = 15ms/4ms/5~30°/2 scanning time= 30 min 0.30x0.30x0.30 mm) as described previously 41,4 . Proton density weighted (PDW) images calculated from VFA-SPGR were segmented using a custom made SHRSP-WKY rat brain template in deriving spatial registration parameters 4 .…”