Reproducibility of a ramping protocol to measure cerebral vascular reactivity using functional magnetic resonance imaging.

Though individual differences in arterial carbon dioxide and oxygen levels inherently exist, the degree of their influence on cerebral vascular reactivity (CVR) is less clear. We examined the reproducibility of BOLD signal changes to an iso-oxic ramping Pet CO2 protocol. CVR changes were induced by altering Pet CO2 while holding Pet O2 constant using a computer-controlled sequential gas delivery (SGD) device. Two MRI scans, each including a linear change in Pet CO2 , were performed using a 3-Tesla (3T) scanner. This ramp sequence consisted of 1 min at 30 mmHg followed by 4 min period during where Pet CO2 was linearly increased from 30 to 50 mmHg, 1 min at 51 mmHg, and concluded with 4 min at baseline. The protocol was repeated at a separate visit with 3 days between visits (minimum). Intraclass correlation coefficients (ICC) and coefficients of variation (CV) were used to verify reproducibility. Eleven subjects (6 females; mean age 26.5 ± 5.7 years) completed the full testing protocol. Good reproducibility was observed for the within-visit ramp sequence (Visit 1: ICC = 0.82, CV = 6.5%; Visit 2: ICC = 0.74, CV = 6.4%). Similarly, ramp sequence were reproducible between visits (Scan 1: ICC = 0.74, CV = 6.5%; Scan 2: ICC = 0.66, CV = 6.1%). Establishing reproducible methodologies for measuring BOLD signal changes in response to Pet CO2 alterations using a ramp protocol will allow researchers to study CVR functionality. Finally, adding a ramping protocol to CVR studies could provide information about changes in CVR over a broad range of Pet CO2 .

Reproducibility of blood oxygen level-dependent signal changes with end-tidal carbon dioxide alterations.

Hypercapnia has been utilized as a stimulus to elicit changes in cerebral blood flow (CBF). However, in many instances it has been delivered in a non-controlled method that is often difficult to reproduce. The purpose of this study was to examine the within- and between-visit reproducibility of blood oxygen level-dependent (BOLD) signal changes to an iso-oxic square wave alteration in end-tidal carbon dioxide partial pressure (Pet CO2 ). Two 3-Tesla (3T) MRI scans were performed on the same visit, with two square wave alterations administered per scan. The protocol was repeated on a separate visit with minimum of 3 days between scanning sessions. Pet CO2 was altered to stimulate changes in cerebral vascular reactivity (CVR), while Pet O2 was held constant. Eleven subjects (six females; mean age 26·5 ± 5·7 years) completed the full testing protocol. Excellent within-visit square wave reproducibility (ICC > 0·75) was observed. Similarly, square waves were reproducible between scanning sessions (ICC > 0·7). This study demonstrates BOLD signal changes in response to alterations in Pet CO2 are reproducible both within- and between-visit MRI scans.

Reproducibility of Brachial Vascular Changes with Alterations in End-Tidal Carbon Dioxide.

The purpose of this study was to examine the reproducibility of the peripheral vascular response to hypercapnia. Healthy college-aged men (n = 7) and women (n = 10) underwent an iso-oxic 10-mm Hg increase in PetCO2 for 12 min. Brachial artery diameter changes were measured using ultrasound imaging. Two tests were completed on day 1 with 15 min of rest between tests. Tests were repeated on day 2. Paired t-tests, Bland-Altman plots and intra-class correlations (ICCs) determined reproducibility. There were no significant differences in peak dilation within day (5.33 ± 3.73% vs. 4.52 ± 2.49%, p = 0.378). The within-day ICC was poor (0.213). Within-day time-to-peak dilation did not significantly differ (660.0 ± 231.8 s vs. 602.7 ± 259.9 s, p = 0.379), and the ICC was fair (0.416, p = 0.113). Between-day peak dilation did not significantly differ (5.24 ± 3.84% vs. 4.71 ± 3.17%, p = 0.123), and the ICC was fair (0.419). Hypercapnia-induced brachial artery dilation is similar within day and between days. The ICC for peak dilation suggests the methodology is not reproducible.

Comparison of brachial dilatory responses to hypercapnia and reactive hyperemia.

Flow-mediated dilation (FMD) relies on reactive hyperemia to stimulate the endothelium to release nitric oxide, causing smooth muscle relaxation. Hypercapnia also produces vasodilation, which is thought to be nitric oxide-independent. The purpose of this study was to compare and contrast the effects of hypercapnia and reactive hyperemia as stimuli for brachial artery dilation. On separate days, twenty-five participants underwent vasodilation studies via reactive hyperemia or hypercapnia (i.e. 10 mmHg increase in end-tidal carbon dioxide [PetCO2)]). During both studies changes in brachial artery diameter were recorded using continuous ultrasound imaging. Heart rate (HR) was measured throughout both tests. Resting HR (63 ± 11 versus 68 ± 14 beats min(-1), p = 0.0027) and baseline brachial artery diameter measurements (4.57 ± 1.51 versus 5.28 ± 1.86 mm, p = 0.022) were significantly different between reactive hyperemia and hypercapnia, respectively. HR at peak dilation (65 ± 11 versus 76 ± 14 beats min(-1), p < 0.0001), peak vessel dilation (8.68 ± 4.50 versus 5.28 ± 1.86%, p = 0.002), and time to peak dilation (90.8 ± 120.1 versus 658.3 ± 226.6 s, p < 0.0001) were also significantly different between reactive hyperemia and hypercapnia. The dynamics by which reactive hyperemia and hypercapnia stimulate vasodilation appear to differ. Hypercapnia produces a smaller and slower vasodilatory effect than reactive hyperemia. Further research is necessary to better understand the mechanisms of vasodilation under hypercapnic conditions.

Bone mineral density in adults with Down syndrome, intellectual disability, and nondisabled adults.

Individuals with intellectual disability (ID) or Down syndrome (DS) may be at greater risk of osteoporosis. The purpose of this study was to compare bone mineral density (BMD) of DS, ID, and non-intellectually disabled (NID) populations. In each group, 33 participants between the ages of 28 and 60 years were compared. BMD was measured with dual-energy x-ray absorptiometry (DXA) scans. BMD (p < .0001) between all groups was significantly different. Participants with DS had significantly lower BMD compared to NID participants. Individuals with ID had significantly lower BMD compared to NID subjects. Participants with DS had the lowest BMD of all groups. DS subjects display a greater risk for osteoporosis than ID subjects or control populations.

Comparison of intima-media thickness of the carotid artery and cardiovascular disease risk factors in adults with versus without the Down syndrome.

Adults with Down syndrome (DS) residing in large institutional settings possess low levels of atherosclerosis. The purpose of this study was to determine whether community-residing adults with DS possess less atherosclerosis than adults without DS. The second purpose was to examine the relation between cardiovascular disease risk factors and intima-media thickness (IMT), a measure of atherosclerosis, in patients with DS. B-mode images of the left common carotid artery were collected to assess IMT in 52 adults with DS and age-, gender-, and race-matched adults without DS (27 women, 25 men; mean age 42 ± 5 years). Total body fat, blood pressure, fasting lipid profiles, insulin, glucose, C-reactive protein, homocysteine, physical activity, and dietary intake were also assessed. Adults with DS possessed lower IMT (0.43 ± 0.07 vs 0.48 ± 0.09 mm, p <0.001), systolic blood pressure (116 ± 15 vs 125 ± 17 mm Hg, p <0.011), and diastolic blood pressure (59 ± 10 vs 73 ± 9 mm Hg, p <0.001) and higher C-reactive protein (0.58 ± 0.55 vs 0.30 ± 0.42 mg/dl, p <0.003), triglycerides (126.5 ± 55.2 vs 103.8 ± 53.2 mg/dl, p <0.048), and total body fat (37.8 ± 10.2% vs 32.4 ± 11.2%, p <0.002) than controls. Male gender (p <0.001) and physical activity (p = 0.020) were identified as predictors of IMT for adults with DS and fasting insulin (p <0.001), age (p <0.001), gender (p <0.001), fruit and vegetable intake (p = 0.001), low-density lipoprotein cholesterol (p = 0.004), and smoking (p = 0.023) for controls. In conclusion, community residing adults with DS may be protected against atherosclerosis despite elevated total body fat and elevated cardiovascular disease risk factors. Predictors of IMT differed for patients with DS compared to controls, which indicates that patients with DS possess a unique model of atherogenesis.