Variability of physiological brain perfusion in healthy subjects – A systematic review of modifiers. Considerations for multi-center ASL studies

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

Brain volumes and cortical thickness on MRI in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER)

BackgroundThe Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a multicenter randomized controlled trial that reported beneficial effects on cognition for a 2-year multimodal intervention (diet, exercise, cognitive training, vascular risk monitoring) versus control (general health advice). This study reports exploratory analyses of brain MRI measures.MethodsFINGER targeted 1260 older individuals from the general Finnish population. Participants were 60-77years old, at increased risk for dementia but without dementia/substantial cognitive impairment. Brain MRI scans were available for 132 participants (68 intervention, 64 control) at baseline and 112 participants (59 intervention, 53 control) at 2years. MRI measures included regional brain volumes, cortical thickness, and white matter lesion (WML) volume. Cognition was assessed at baseline and 1- and 2-year visits using a comprehensive neuropsychological test battery. We investigated the (1) differences between the intervention and control groups in change in MRI outcomes (FreeSurfer 5.3) and (2) post hoc sub-group analyses of intervention effects on cognition in participants with more versus less pronounced structural brain changes at baseline (mixed-effects regression models, Stata 12).ResultsNo significant differences between the intervention and control groups were found on the changes in MRI measures. Beneficial intervention effects on processing speed were more pronounced in individuals with higher baseline cortical thickness in Alzheimer's disease signature areas (composite measure of entorhinal, inferior and middle temporal, and fusiform regions). The randomization groupxtimexcortical thickness interaction coefficient was 0.198 (p=0.021). A similar trend was observed for higher hippocampal volume (groupxtimexhippocampus volume interaction coefficient 0.1149, p=0.085).ConclusionsThe FINGER MRI exploratory sub-study did not show significant differences between the intervention and control groups on changes in regional brain volumes, regional cortical thicknesses, or WML volume after 2years in at-risk elderly without substantial impairment. The cognitive benefits on processing speed of the FINGER intervention may be more pronounced in individuals with fewer structural brain changes on MRI at baseline. This suggests that preventive strategies may be more effective if started early, before the occurrence of more pronounced structural brain changes.Trial registrationClinicalTrials.gov, NCT01041989. Registered January 5, 2010.Peer reviewe

New Insights into Alzheimer's Disease Progression: A Combined TMS and Structural MRI Study

BACKGROUND: Combination of structural and functional data of the human brain can provide detailed information of neurodegenerative diseases and the influence of the disease on various local cortical areas. METHODOLOGY AND PRINCIPAL FINDINGS: To examine the relationship between structure and function of the brain the cortical thickness based on structural magnetic resonance images and motor cortex excitability assessed with transcranial magnetic stimulation were correlated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients as well as in age-matched healthy controls. Motor cortex excitability correlated negatively with cortical thickness on the sensorimotor cortex, the precuneus and the cuneus but the strength of the correlation varied between the study groups. On the sensorimotor cortex the correlation was significant only in MCI subjects. On the precuneus and cuneus the correlation was significant both in AD and MCI subjects. In healthy controls the motor cortex excitability did not correlate with the cortical thickness. CONCLUSIONS: In healthy subjects the motor cortex excitability is not dependent on the cortical thickness, whereas in neurodegenerative diseases the cortical thinning is related to weaker cortical excitability, especially on the precuneus and cuneus. However, in AD subjects there seems to be a protective mechanism of hyperexcitability on the sensorimotor cortex counteracting the prominent loss of cortical volume since the motor cortex excitability did not correlate with the cortical thickness. Such protective mechanism was not found on the precuneus or cuneus nor in the MCI subjects. Therefore, our results indicate that the progression of the disease proceeds with different dynamics in the structure and function of neuronal circuits from normal conditions via MCI to AD

Excess of visceral adipose tissue with or without aortic elongation leads to a steeper heart position

Abstract Background: The heart’s position determined as the heart–aorta angle (HAA) has been demonstrated to associate with ascending aortic (AA) dilatation. Visceral adipose tissue (VAT) and aortic elongation may shift the heart to the steeper position. Purpose: To investigate whether VAT and aortic length influence the HAA. Material and methods: We examined 346 consecutive patients (58.4% men; mean age = 67.0 ± 14.1 years) who underwent aortic computed tomography angiography (CTA). HAA was measured as the angle between the long axis of the heart and AA midline. The amount of VAT was measured at the level of middle L4 vertebra from a single axial CT slice. Aortic length was measured by combining four anatomical segments in different CTA images. The amount of VAT and aortic length were determined as mild with values in the lowest quartile and as excessive with values in the other three quartiles. Results: A total of 191 patients (55.2%) had no history of aortic diseases, 134 (38.7%) displayed AA dilatation, 8 (2.3%) had abdominal aortic aneurysm (AAA), and 13 (3.8%) had both AA dilatation and AAA. There was a strong nonlinear regression between smaller HAA and VAT/height, and HAA and aortic length/height. Median HAA was 124.2° (interquartile range 119.0°–130.8°) in patients with a mild amount of VAT versus 120.5° (interquartile range 115.4°–124.7°) in patients with excessive VAT (P < 0.001). Conclusion: An excessive amount of VAT and aortic elongation led to a steeper heart position. These aspects may possess clinical value when evaluating aortic diseases in obese patients

Pulmonary artery dilatation Is a common finding in a coronary artery CT angiography population

Abstract Background/Aim: Dilatation of the main pulmonary artery (mPA) is a common incidental finding in chest imaging and often leads to consultation. The aim of this study was to determine the prevalence of mPA dilatation in a coronary artery CT angiography (CCTA) population. Patients and Methods: The study investigated 985 consecutive patients scheduled for diagnostic CCTA. The transverse axial diameter of the mPA was measured. The prevalence of mPA dilatation was estimated using different reference values (Framingham Heart Study: 28.9 mm for males and 26.9 mm for females, Bozlar: 29.5 mm for both genders and Karazincir: 32.6 mm for males and 31.9 mm for females). Results: The patient mean age was 53.0±9.7 years (66.5% were women). Body surface area (BSA) correlated moderately with the mPA diameter (r=0.423, p<0.001). The prevalence of mPA dilatation varied from 5.9% (Karazincir) to 33.7% (Framingham Heart Study) in the overall study population. Conclusion: The prevalence of mPA dilatation is high in a CCTA patient population when using a cut-off value from the Framingham Heart Study

Aortic dilatation associates with flow displacement and increased circumferential wall shear stress in patients without aortic stenosis:a prospective clinical study

Abstract Background: The relationship between blood flow characteristics and ascending aortic (AA) dilatation has not been studied in patients with a tricuspid aortic valve (TAV) without aortic stenosis. Purpose: To evaluate whether 4D flow characteristics determined in MRI are related to AA dilatation by comparing dilated AA and nondilated AA subjects with TAV. Study Type: Prospective. Population: Twenty patients with dilated AA and 20 age‐matched patients with nondilated AA. Field Strength/Sequence: 1.5T/4D flow, 2D flow, and anatomic images. Assessment: Altogether, 16 different 4D flow parameters were assessed in 10 planes in the thoracic aorta. Intra‐ and interobserver reproducibility were analyzed. Statistical Tests: Independent t‐test for normally distributed and the Mann–Whitney test for skewed distributed parameters were used. A paired‐samples t‐test was used to compare 2D and 4D flow parameters. Intraclass correlation coefficient (ICC) was used in intra‐ and interobserver reproducibility analysis. Results: Aortic flow was displaced from the centerline of the aorta in the proximal and tubular planes. Flow displacement (FD) was greatest in the proximal plane of AA and was higher in dilated AA (4.5%, range 3.0–5.8%) than in nondilated AA (2.0%, 1.0–3.0%, P < 0.001). Total wall shear stress (WSS) values were 1.3 ± 0.4 times higher on the displaced side than on the opposite side of the aorta (P < 0.01). The circumferential WSS (WSSC) ratio to total WSS was greater in dilated AA, being 0.48 ± 0.11 vs. 0.32 ± 0.09 in the inner curvature of the proximal AA (P < 0.001) and 0.37 ± 0.11 vs. 0.26 ± 0.07 in the whole aortic ring in the distal AA (P < 0.001). Depending on 4D flow parameters, reproducibility varied from excellent (ICC = 0.923) to very low (ICC = 0.204). Data Conclusion: The present study demonstrates that 4D flow measurements help to visualize the pathological flow patterns related to aortic dilatation. Flow displacement and an increased WSSc/WSS ratio are significantly associated with AA dilatation

Flow displacement and decreased wall shear stress might be associated with the growth rate of an ascending aortic dilatation

Abstract Objectives: Our goal was to evaluate whether four-dimensional (4D) flow magnetic resonance imaging (MRI) can predict the growth rate of dilatation of the ascending aorta (AA) in patients with a tricuspid, normally functioning aortic valve. Methods: In this prospective clinical study, aortic 4D flow MRI was performed at the Kuopio University Hospital on 30 patients diagnosed with AA dilatation (maximum diameter >40 mm) between August 2017 and July 2020. The MRI was repeated after a 1-year follow-up, with AA dimensions and 4D flow parameters analysed retrospectively at both time points. The standard error of measurement was used to assess the statistical significance of the growth rate of AA dilatation. Flow displacement (FD) was transformed to a class-scaled parameter using FD ≥5% as a threshold. Results: Statistically significant growth [median 2.1 mm (1.5–2.2 mm); P = 0.03] was detected in 6 male patients (20%); the AA diameter remained unchanged [0.2 mm (−0.3 to 0.9 mm)] in 24 patients (80%). An increased FD at the baseline was associated with significant growth during the 1-year follow-up in the proximal AA. An association was detected between decreased total wall shear stress and significant aortic growth in the inner curve of the sinotubular junction [529 mPa (449–664 mPa) vs 775 mPa (609–944 mPa); P = 0.03] and the anterior side of the proximal aortic arch [356 mPa (305–367 mPa) vs 493 mPa (390–586 mPa); P < 0.001]. Conclusions: FD and decreased wall shear stress seem to be associated with significant growth of AA dilatation at the 1-year follow-up. Thus, 4D flow MRI might be useful in assessing risk for AA diameter growth in patients with a tricuspid aortic valve

A smaller heart-aorta-angle associates with ascending aortic dilatation and increases wall shear stress

Abstract Objectives: The aim of this study was to evaluate whether the orientation of the heart, measured as an angle between the long axis of the heart and ascending aorta midline (heart-aorta-angle, HAA), associates with ascending aortic (AA) dilatation. Furthermore, the association between HAA and wall shear stress (WSS) was studied. Methods: HAA was retrospectively measured in 1000 consecutive coronary artery computed tomographic angiography (CCTA) images in patients with low-to-moderate pretest probability for coronary artery disease (CAD). To evaluate the effects of HAA on AA flow, 4D flow MRI was performed for 28 patients with AA dilatation (> 40 mm) and WSS was analyzed. Results: The mean age of patients undergoing CCTA was 52.9 ± 9.8 years; 66.5% were women. Their median HAA was 128.7° and interquartile range 123.3–134.1°. HAA was significantly smaller in patients with dilated AA (median 126.7° [121.3–130.8°]) compared with the patients with normal AA (median 129.5° [124.3–135.3°], p < 0.001). HAA was smaller in males (p < 0.001) and in patients with diabetes (p = 0.016), hypertension (p = 0.001), CAD (p = 0.003), hypercholesterolemia (p < 0.001), and bicuspid aortic valve (p = 0.025) than without these factors. In a subpopulation without any of these underlying diseases (n = 233), HAA was still significantly smaller in the patients with dilated AA (median 127.9° [124.3–134.3°]) compared with patients with normal AA (median 131.9° [127.6–136.9°], p = 0.013). In 4D flow MRI, a smaller HAA correlated with increased total WSS in the outer curvature of the proximal AA (r = − 0.510, p = 0.006). Conclusions: A smaller HAA associates with AA dilatation and affects the blood flow in the proximal AA

High prevalence of ascending aortic dilatation in a consecutive coronary CT angiography patient population

Abstract Objectives: To clarify the prevalence and risk factors of ascending aortic (AA) dilatation according to ESC 2014 guidelines. Methods: This study included 1000 consecutive patients scheduled for diagnostic coronary artery computed tomographic angiography. AA diameter was retrospectively measured in 3 planes: sinus valsalva, sinotubular junction, and tubular part. The threshold for AA dilatation was set to > 40 mm which has been suggested as an upper normal limit for AA diameter in ESC 2014 guidelines on aortic diseases. Aortic size index (ASI) using the ratio between aortic diameter and body surface area (BSA) was applied as a comparative measurement. The threshold for AA dilatation was set to the upper limit of normal distribution exceeding two standard deviations (95%). Risk factors for AA dilatation were collected from medical records. Results: The patients’ mean age was 52.9 ± 9.8 years (66.5% women). The prevalence of AA dilatation was 23.0% in the overall study population (52.5% males) and 15.1% in the subgroup of patients with no coronary artery disease or bicuspid (BAV)/mechanical aortic valve (n = 365). According to the normal-distributed ASI values, the threshold for sinus valsalva was defined as 23.2 mm/m2 and for tubular part 22.2 mm/m2 in the subgroup. Higher BSA was associated with larger AA dimensions (r = 0.407, p < 0.001). Male gender (p < 0.001), BAV (p < 0.001), hypertension (p = 0.009) in males, and smoking (p < 0.001) appeared as risk factors for AA dilatation. Conclusions: The prevalence of AA dilatation is high with current ESC guidelines for normal AA dimension, especially in males. Body size is strongly associated with AA dimensions; it would be more reliable to use BSA-adjusted AA diameters for the definition of AA dilatation

Grey matter atrophy in patients with benign multiple sclerosis

Abstract Background: Brain atrophy appears during the progression of multiple sclerosis (MS) and is associated with the disability caused by the disease. Methods: We investigated global and regional grey matter (GM) and white matter (WM) volumes, WM lesion load, and corpus callosum index (CCI), in benign relapsing-remitting MS (BRRMS, n = 35) with and without any treatment and compared those to aggressive relapsing-remitting MS (ARRMS, n = 46). Structures were analyzed by using an automated MRI quantification tool (cNeuro®). Results: The total brain and cerebral WM volumes were larger in BRRMS than in ARRMS (p = .014, p = .017 respectively). In BRRMS, total brain volumes, regional GM volumes, and CCI were found similar whether or not disease-modifying treatment (DMT) was used. The total (p = .033), as well as subcortical (p = .046) and deep WM (p = .041) lesion load volumes were larger in BRRMS patients without DMT. Cortical GM volumes did not differ between BRRMS and ARRMS, but the volumes of total brain tissue (p = .014) and thalami (p = .003) were larger in patients with BRRMS compared to ARRMS. A positive correlation was found between CCI and whole-brain volume in both BRRMS (r = .73, p < .001) and ARRMS (r = .80, p < .01). Conclusions: Thalamic volume is the most prominent measure to differentiate BRRMS and ARRMS. Validation of automated quantification of CCI provides an additional applicable MRI biomarker to detect brain atrophy in MS