In the evaluation of cerebrovascular CO2 reactivity measurements, it is often assumed that the diameter of the large intracranial arteries insonated by transcranial Doppler remains unaffected by changes in arterial CO2 partial pressure. However, the strong cerebral vasodilatory capacity of CO2 challenges this assumption, suggesting that there should be some changes in diameter, even if very small. Data from previous studies on effects of CO2 on cerebral artery diameter [middle cerebral artery (MCA)] have been inconsistent. In this study, we examined 10 healthy subjects (5 women, 5 men, age 21-30 yr). High-resolution (0.2 mm in-plane) MRI scans at 7 Tesla were used for direct observation of the MCA diameter during hypocapnia, -1 kPa (-7.5 mmHg), normocapnia, 0 kPa (0 mmHg), and two levels of hypercapnia, +1 and +2 kPa (7.5 and 15 mmHg), with respect to baseline. The vessel lumen was manually delineated by two independent observers. The results showed that the MCA diameter increased by 6.8 ± 2.9% in response to 2 kPa end-tidal P(CO2) (PET(CO2)) above baseline. However, no significant changes in diameter were observed at the -1 kPa (-1.2 ± 2.4%), and +1 kPa (+1.4 ± 3.2%) levels relative to normocapnia. The nonlinear response of the MCA diameter to CO2 was fitted as a continuous calibration curve. Cerebral blood flow changes measured by transcranial Doppler could be corrected by this calibration curve using concomitant PET(CO2) measurements. In conclusion, the MCA diameter remains constant during small deviations of the PET(CO2) from normocapnia, but increases at higher PET(CO2) values.

The longitudinal relaxation time of blood is a crucial parameter for quantification of cerebral blood flow by arterial spin labeling and is one of the main determinants of the signal-to-noise ratio of the resulting perfusion maps. Whereas at low and medium magnetic field strengths (B0), its in vivo value is well established; at ultra-high field, this is still uncertain. In this study, longitudinal relaxation time of blood in the sagittal sinus was measured at 1.5 T, 3 T, and 7 T. A nonselective inversion pulse preceding a Look-Locker echo planar imaging sequence was performed to obtain the inversion recovery curve of venous blood. The results showed that longitudinal relaxation time of blood at 7 T was ∼ 2.1 s which translates to an anticipated 33% gain in the signal-to-noise ratio in arterial spin labeling experiments due to T1 relaxation alone compared with 3 T. In addition, the linear relationship between longitudinal relaxation time of blood and B0 was confirmed.

Summary Background Previous work suggests that impairments of cerebrovascular flow or reactivity might be early markers of cerebral amyloid angiopathy (CAA). Hereditary cerebral hemorrhage with amyloidosis–Dutch type (HCHWA-D) is a genetic form of CAA that can diagnosed early by DNA testing, allowing study of CAA before onset of clinical symptoms. The aim of the present study was to investigate whether hemodynamic measures are decreased in HCHWA-D mutation carriers compared to healthy controls. Methods In this case-control study, we included pre-symptomatic and symptomatic HCHWA-D mutation carriers diagnosed through genetic testing and recruited through the HCHWA-D patient association (Katwijk, Netherlands) and the outpatient clinic of the Department of Neurology of the Leiden University Medical Center (Leiden, Netherlands), and healthy controls. Regional cerebral blood flow (rCBF) was measured using pseudo-continuous arterial spin labeling. Quantitative flow was determined by phase-contrast MR angiography of the cerebropetal vessels. Vascular reactivity was determined by measuring changes in the blood oxygen level-dependent (BOLD) signal after visual stimulation. Data from pre-symptomatic and symptomatic individuals were compared with healthy controls using mixed-model regression analysis. Results In the study done between May 15, 2012 and December 22, 2015, we investigated imaging data from 27 HCHWA-D mutation carriers (12 pre-symptomatic and 15 symptomatic) and 33 healthy controls. Compared with controls, symptomatic HCHWA-D carriers had significantly decreased cortical gray matter rCBF in the occipital lobe (mean difference −11.1 ml/100g/min, CI −2.8 to −19.3, p=0.010) and decreased flux in the basilar artery (mean difference −0.9ml/s, CI −1.5 to −0.2, p=0.019). However, no changes were observed in the rCBF and flux in pre-symptomatic carriers compared with controls. Vascular reactivity was significantly decreased in the occipital lobe in both pre-symptomatic (BOLD amplitude 1.1±0.5% change, mean difference −0.4% change, CI −0.7 to −0.2, p=0.001; time to baseline 10.1±7.6 s, mean difference 4.6 s, CI 0.4 to 8.8, p=0.032) and symptomatic carriers (BOLD amplitude 0.4±0.1% change, mean difference −0.9% change, CI −1.1 to −0.6, p<0.0001; TTP 14.8±8.6 s, mean difference 12.2 s, CI 8.6 to 15.9,p<0.0001; TTB 20.3±8.4 s, mean difference 13.1s, CI 9.4 to 16.9, p<0.0001) compared with controls. Interpretation Vascular reactivity in the occipital lobe was decreased in both symptomatic and pre-symptomatic individuals with HCHWA-D. This indicates that determination of vascular reactivity might be a useful biomarker for early detection of vascular amyloid pathology in sporadic CAA, and a biomarker of efficacy in future intervention trials. Funding National Institutes of Health.

Adjusting the timing of encoding blocks in te-pCASL allows for tailoring the acquisition to specific applications. With the free lunch setup, te-pCASL delivers CBF and high resolution ATT maps within a single scan, with a small penalty in tSNR.

Quantitative measurements of brain perfusion are influenced by perfusion-modifiers. Standardization of measurement conditions and correction for important modifiers is essential to improve accuracy and to facilitate the interpretation of perfusion-derived parameters. An extensive literature search was carried out for factors influencing quantitative measurements of perfusion in the human brain unrelated to medication use. A total of 58 perfusion modifiers were categorized into four groups. Several factors (e.g., caffeine, aging, and blood gases) were found to induce a considerable effect on brain perfusion that was consistent across different studies; for other factors, the modifying effect was found to be debatable, due to contradictory results or lack of evidence. Using the results of this review, we propose a standard operating procedure, based on practices already implemented in several research centers. Also, a theory of ‘deep MRI physiotyping’ is inferred from the combined knowledge of factors influencing brain perfusion as a strategy to reduce variance by taking both personal information and the presence or absence of perfusion modifiers into account. We hypothesize that this will allow to personalize the concept of normality, as well as to reach more rigorous and earlier diagnoses of brain disorders.