The association between frailty and MRI features of cerebral small vessel disease

Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype

Hemodynamic provocation with acetazolamide shows impaired cerebrovascular reserve in adults with sickle cell disease

Sickle cell disease is characterized by chronic hemolytic anemia and vascular inflammation, which can diminish the vasodilatory capacity of the small resistance arteries, making them less adept at regulating cerebral blood flow. Autoregulation maintains adequate oxygen delivery, but when vasodilation is maximized, the low arterial oxygen content can lead to ischemia and silent cerebral infarcts. We used magnetic resonance imaging of cerebral blood flow to quantify whole-brain cerebrovascular reserve in 36 adult patients with sickle cell disease (mean age, 31.9 +/- 11.3 years) and 11 healthy controls (mean age, 37.4 +/- 15.4 years), and we used high-resolution 3D FLAIR magnetic resonance imaging to determine the prevalence of silent cerebral infarcts. Cerebrovascular reserve was calculated as the percentage change in cerebral blood flow after a hemodynamic challenge with acetazolamide. Co-registered lesion maps were used to demonstrate prevalent locations for silent cerebral infarcts. Cerebral blood flow was elevated in patients with sickle cell disease compared to controls (median [interquartile range]: 82.8 [20.1] vs. 51.3 [4.8] mL/100g/min, P<0.001). Cerebral blood flow was inversely associated with age, hemoglobin, and fetal hemoglobin, and correlated positively with bilirubin, and LDH, indicating that cerebral blood flow may reflect surrogates of hemolytic rate. Cerebrovascular reserve in sickle cell disease was decreased by half compared to controls (34.1 [33.4] vs. 69.5 [32.4] %, P<0.001) and was associated with hemoglobin and erythrocyte count indicating anemia-induced hemodynamic adaptations. In total, 29/36 patients (81%) and 5/11 controls (45%) had silent cerebral infarcts (median volume of 0.34 vs. 0.02 mL, P=0.03). Lesions were preferentially located in the borderzone. In conclusion, patients with sickle cell disease have a globally reduced cerebrovascular reserve as determined by arterial spin labeling with acetazolamide and reflects anemia-induced impaired vascular function in sickle cell disease

In Vivo T1 of Blood Measurements in Children with Sickle Cell Disease Improve Cerebral Blood Flow Quantification from Arterial Spin-Labeling MRI

Children with sickle cell disease have low hematocrit and elevated CBF, the latter of which can be assessed with arterial spin-labeling MR imaging. Quantitative CBF values are obtained by using an estimation of the longitudinal relaxation time of blood (T1blood). Because T1blood depends on hematocrit in healthy individuals, we investigated the importance of measuring T1blood in vivo with MR imaging versus calculating it from hematocrit or assuming an adult fixed value recommended by the literature, hypothesizing that measured T1blood would be the most suited for CBF quantification in children with sickle cell disease. Four approaches for T1blood estimation were investigated in 39 patients with sickle cell disease and subsequently used in the CBF quantification from arterial spin-labeling MR imaging. First, we used 1650 ms as recommended by the literature (T1blood-fixed); second, T1blood calculated from hematocrit measured in patients (T1blood-hematocrit); third, T1blood measured in vivo with a Look-Locker MR imaging sequence (T1blood-measured); and finally, a mean value from T1blood measured in this study in children with sickle cell disease (T1blood-sickle cell disease). Quantitative flow measurements acquired with phase-contrast MR imaging served as reference values for CBF. T1blood-measured (1818 ± 107 ms) was higher than the literature recommended value of 1650 ms, was significantly lower than T1blood-hematocrit (2058 ± 123 ms, P < .001), and, most interesting, did not correlate with hematocrit measurements. Use of either T1blood-measured or T1blood-sickle cell disease provided the best agreement on CBF between arterial-spin labeling and phase-contrast MR imaging reference values. This work advocates the use of patient-specific measured T1blood or a standardized value (1818 ms) in the quantification of CBF from arterial spin-labeling in children with SC

Photon vs. proton radiochemotherapy: Effects on brain tissue volume and perfusion

Neuro Imaging Researc

Comparison of arterial spin labeling registration strategies in the multi-center GENetic frontotemporal dementia initiative (GENFI)

Neuro Imaging Researc

The association between frailty and MRI features of cerebral small vessel disease

Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype.Ophthalmic researc

Arterial spin labeling perfusion MRI: Inter-vendor reproducibility and clinical applicability

Arterial spin labeling (ASL) is a perfusion magnetic resonance imaging (MRI) technique that non-invasively measures cerebral blood flow (CBF). The first part of this thesis concerns the inter-vendor reproducibility of ASL. Studies in this thesis show that on a total gray matter (GM) level, long-term physiological perfusion fluctuation dominates technical differences between ASL sequences and scanners. However, CBF data from smaller regions of interest were only comparable when sequences were made as identical as possible on different vendor MRI systems. Major effects include different readout modules, differences in effective post-labeling delay leading to differences in transit time sensitivity, the extent of the point spread function and the efficiency of background suppression. Furthermore, slight differences in sequence parameters can have a larger effect than differences in MRI hardware. The second part of this thesis investigates several potential clinical applications of ASL. We show that white matter (WM) perfusion signal can be measured in the elderly, but also that the WM region of interest should be carefully eroded to avoid contamination with GM CBF. We demonstrate the statistical benefits of modest vascular crushing in a large population of elderly with hypertension. In the same population, WM lesion volume was correlated with WM lesion CBF but not with normal appearing WM or GM CBF. In children with sickle cell disease, we show correlations between CBF and hematological parameters that are both involved in the pathogenesis of WML and are key targets in the treatment of this disease