Effects of motion and retrospective motion correction on the visualization and quantification of perivascular spaces in ultrahigh resolution T2-weighted images at 7T.

PURPOSE: Motion can strongly affect MRI image quality and derived imaging measures. We studied the effects of motion and retrospective motion correction (MC) on the visualization and quantitative measures of the perivascular space and penetrating vessel (PVSV) complex, an essential part of the glymphatic system, on high-resolution T2 -weighted MRI images at 7T. METHODS: MC was achieved by adjusting k-space data based on head positions measured using fat navigator images. PVSV visibility and quantitative measures including diameter, volume fraction (VF), count, and contrast were compared between images with and without MC. RESULTS: Without MC, VF, and count decreased significantly with increasing head rotation. MC improved PVSV visualization in all cases with severe motion artifacts. MC decreased diameter in white matter (WM) and increased VF, count, and contrast in basal ganglia and WM. The changes of VF, count, and contrast after MC strongly correlated with motion severity. MC eliminated the significant dependences of VF and count on rotation and reduced the inter-subject variations of VF and count. The effect sizes of age and breathing gas effects on VF and count, and contrast increased in most cases after MC, while those on diameter exhibited inconsistent behavior. CONCLUSIONS: Motion affects PVSV quantification without MC. MC improves PVSV visibility and increases the statistical power of detecting physiological PVSV VF, count, and contrast changes but may have limited benefits for increasing the power for detecting diameter changes.

Morphology of perivascular spaces and enclosed blood vessels in young to middle-aged healthy adults at 7T: Dependences on age, brain region, and breathing gas.

Perivascular spaces (PVSs) are fluid-filled spaces surrounding penetrating blood vessels in the brain and are an integral pathway of the glymphatic system. A PVS and the enclosed blood vessel are commonly visualized as a single vessel-like complex (denoted as PVSV) in high-resolution MRI images. Quantitative characterization of the PVSV morphology in MRI images in healthy subjects may serve as a reference for detecting disease related PVS and/or blood vessel alterations in patients with brain diseases. To this end, we evaluated the age dependences, spatial heterogeneities, and dynamic properties of PVSV morphological features in 45 healthy subjects (21-55 years old), using an ultra-high-resolution three-dimensional transverse relaxation time weighted MRI sequence (0.41 â€‹× â€‹0.41 â€‹× â€‹0.4 â€‹mm3) at 7T. Quantitative PVSV parameters, including apparent diameter, count, volume fraction (VF), and relative contrast to noise ratio (rCNR) were calculated in the white matter and subcortical structures. Dynamic changes were induced by carbogen breathing which are known to induce vasodilation and increase the blood oxygenation level in the brain. PVSV count and VF significantly increased with age in basal ganglia (BG), so did rCNR in BG, midbrain, and white matter (WM). Apparent PVSV diameter also showed a positive association with age in the three brain regions, although it did not reach statistical significance. The PVSV VF and count showed large inter-subject variations, with coefficients of variation ranging from 0.17 to 0.74 after regressing out age and gender effects. Both apparent diameter and VF exhibited significant spatial heterogeneity, which cannot be explained solely by radio-frequency field inhomogeneities. Carbogen breathing significantly increased VF in BG and WM, and rCNR in thalamus, BG, and WM compared to air breathing. Our results are consistent with gradual dilation of PVSs with age in healthy adults. The PVSV morphology exhibited spatial heterogeneity and large inter-subject variations and changed during carbogen breathing compared to air breathing.

Evaluation of renal oxygenation change under the influence of carbogen breathing using a dynamic R2 , R2 ' and R2 * quantification approach.

The purpose of this study is to demonstrate the feasibility of dynamic renal R2 /R2 '/R2 * measurements based on a method, denoted psMASE-ME, in which a periodic 180° pulse-shifting multi-echo asymmetric spin echo (psMASE) sequence, combined with a moving estimation (ME) strategy, is adopted. Following approval by the institutional animal care and use committee, a block design of respiratory challenge with interleaved air and carbogen (97% O2 , 3% CO2 ) breathing was employed in nine rabbits. Parametrical R2 /R2 '/R2 * maps were computed and average R2 /R2 '/R2 * values were measured in regions of interest in the renal medulla and cortex. Bland-Altman plots showed good agreement between the proposed method and reference standards of multi-echo spin echo and multi-echo gradient echo sequences. Renal R2 , R2 ' and R2 * decreased significantly from 16.2 ± 4.4 s-1 , 9.8 ± 5.2 s-1 and 25.9 ± 5.0 s-1 to 14.9 ± 4.4 s-1 (p < 0.05), 8.5 ± 4.1 s-1 (p < 0.05) and 23.4 ± 4.8 s-1 (p < 0.05) in the cortex when switching the gas mixture from room air to carbogen. In the renal medulla, R2 , R2 ' and R2 * also decreased significantly from 12.9 ± 4.7 s-1 , 15.1 ± 5.8 s-1 and 27.9 ± 5.3 s-1 to 11.8 ± 4.5 s-1 (p < 0.05), 14.2 ± 4.2 s-1 (p < 0.05) and 25.8 ± 5.1 s-1 (p < 0.05). No statistically significant differences in relative R2 , R2 ' and R2 * changes were observed between the cortex and medulla (p = 0.72 for R2 , p = 0.39 for R2 ' and p = 0.61 for R2 *). The psMASE-ME method for dynamic renal R2 /R2 '/R2 * measurements, together with the respiratory challenge, has potential use in the evaluation of renal oxygenation in many renal diseases.

Noninvasive measurement of renal oxygen extraction fraction under the influence of respiratory challenge.

PURPOSE: To demonstrate the feasibility of using a susceptibility-based magnetic resonance imaging (MRI) technique for measuring renal oxygen extraction fraction (OEF) changes under the influence of carbogen (97% O2 , 3% CO2 ) breathing. MATERIALS AND METHODS: Eight New Zealand White rabbits were included in this study with local animal care committee approval. For OEF measurement, an asymmetric spin echo (ASE) sequence was used to acquire source images and a susceptibility model was utilized for OEF estimation at 3.0T. Within-session and between-day tests were conducted to evaluate the reproducibility of this OEF measurement. OEF changes were measured under respiratory challenge with alternated air and carbogen (97% O2 , 3% CO2 ) breathing. For comparison, blood samples were collected for the measurement of pO2 . RESULTS: The within-session coefficients of variation (CVs) of renal OEF measurements were 6.62% in cortex and 5.92% in medulla, while between-day CVs were 7.52% in cortex and 8.03% in medulla. Under carbogen breathing, renal OEFs decreased significantly from 0.32 ± 0.03 to 0.28 ± 0.02 (P < 0.01) in cortex, and from 0.34 ± 0.04 to 0.31 ± 0.03 (P < 0.01) in medulla. No statistical difference of relative OEF change was seen between cortex and medulla (P = 0.93). In addition, negative correlation between renal OEF and blood pO2 was found (r = 0.68 (P < 0.05) in cortex, and r = 0.64 (P < 0.05) in medulla). CONCLUSION: This study demonstrates the feasibility of using a susceptibility-based OEF measurement method for the evaluation of renal oxygenation changes induced by carbogen breathing. J. Magn. Reson. Imaging 2016;44:230-237.

Targeting Hypoxia: Revival of Old Remedies.

Tumour hypoxia is significantly correlated with patient survival and treatment outcomes. At the molecular level, hypoxia is a major driving factor for tumour progression and aggressiveness. Despite the accumulative scientific and clinical efforts to target hypoxia, there is still a need to find specific treatments for tumour hypoxia. In this review, we discuss a variety of approaches to alter the low oxygen tumour microenvironment or hypoxia pathways including carbogen breathing, hyperthermia, hypoxia-activated prodrugs, tumour metabolism and hypoxia-inducible factor (HIF) inhibitors. The recent advances in technology and biological understanding reveal the importance of revisiting old therapeutic regimens and repurposing their uses clinically.