Improved Assessment of Longitudinal Spinal Cord Atrophy in Multiple Sclerosis Using a Registration-Based Approach: Relevance for Clinical Studies.

BACKGROUND: Reliable measurements of cervical cord atrophy progression may be useful for monitoring neurodegeneration in multiple sclerosis (MS). PURPOSE: To compare a new, registration-based (Reg) method with two existing methods (active surface [AS] and propagation segmentation [PropSeg]) to measure cord atrophy changes over time in MS. STUDY TYPE: Retrospective. SUBJECTS: Cohort I: Eight healthy controls (HC) and 28 MS patients enrolled at a single institution, and cohort II: 25 HC and 63 MS patients enrolled at three European sites. FIELD STRENGTH/SEQUENCE: 3D T1-weighted gradient echo sequence, acquired at 1.5 T (cohort I) and 3.0 T (cohort II). ASSESSMENT: Percentage cord area changes (PCACs) between baseline and follow-up (cohort I: 2.34 years [interquartile range = 2.00-2.55 years], cohort II: 1.05 years [interquartile range = 1.01-1.18 years]) were evaluated for all subjects using Reg, AS, and PropSeg. Reg included an accurate registration of baseline and follow-up straightened cord images, followed by AS-based optimized cord segmentation. A subset of studies was analyzed twice by two observers. STATISTICAL TESTS: Linear regression models were used to estimate annualized PCAC, and effect sizes expressed as the ratio between the estimated differences and HC error term (P < 0.05). Reproducibility was assessed by linear mixed-effect models. Annualized PCACs were used for sample size calculations (significance: α = 0.05, power: 1 - ß = 0.80). RESULTS: Annualized PCACs and related standard errors (SEs) were lower with Reg than with other methods: PCAC in MS patients at 1.5 T was -1.12% (SE = 0.22) with Reg, -1.32% (SE = 0.30) with AS, and -1.40% (SE = 0.33) with PropSeg, while at 3.0 T PCAC was -0.83% (SE = 0.25) with Reg, -0.92% (SE = 0.32) with AS, and -1.18 (SE = 0.53) with PropSeg. This was reflected in larger effect sizes and lower sample sizes. Intra- and inter-observer agreement range was 0.72-0.91 with AS, and it was >0.96 with Reg. DATA CONCLUSION: The results support the use of the registration method to measure cervical cord atrophy progression in future MS clinical studies. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Brain tissue motion in acute hemorrhagic stroke using amplified MRI (aMRI).

Brain tissue pulsates with each cardiac cycle, however the effect of disease on this natural motion is still unclear. Current literature mainly focuses on healthy brain tissue, with only limited studies looking at disease states such as Chiari malformation and acute ischemic stroke. This case report advances on recent literature by describing the case of a patient with an acute intracerebral hemorrhage and demonstrating an amplified MRI cine of the brain's motion. A clearer understanding of the effects of disease on brain motion may guide clinical application of pulsation measurement.

Neurological impact of emboli during adult cardiac surgery.

OBJECTIVES: This study draws on advances in Doppler ultrasound bubble sizing to investigate whether high volumes of macro-bubbles entering the brain during cardiac surgery increase the risk of new cerebral microbleeds (CMBs), ischemic MR lesions, or post-operative cognitive decline (POCD). METHODS: Transcranial Doppler (TCD) ultrasound recordings were analysed to estimate numbers of emboli and macrobubbles (>100 µm) entering the brain during cardiac surgery. Logistic regression was used to explore the hypothesis that emboli characteristics affect the incidence of new brain injuries identified through pre- and post-operative MRI and neuropsychological testing. RESULTS: TCD, MRI, and neuropsychological test data were compared between 28 valve and 18 CABG patients. Although valve patients received over twice as many emboli per procedure [median: 1995 vs. 859, p = .004], and seven times as many macro-bubbles [median: 218 vs. 28, p = .001], high volumes of macrobubbles were not found to be significantly associated with new CMBs, new ischaemic lesions, or POCD. The odds of acquiring new CMBs increased by approximately 5% [95% CI: 1 to 10%] for every embolus detected in the first minute after the release of the aortic cross-clamp (AxC). Logistic regression models also confirmed previous findings that cardiopulmonary bypass time and valve surgery were significant predictors for new CMBs (both p = .03). Logistic regression analysis estimated an increase in the odds of acquiring new CMBs of 6% [95% CI: 1 to 12%] for every minute of bypass time over 91 mins. CONCLUSIONS: This small study provides new information about the properties and numbers of bubbles entering the brain during surgery, but found no evidence to substantiate a direct link between large numbers of macrobubbles and adverse cognitive or MR outcome. Clinical Trial Registration URL - http://www.isrctn.com. Unique identifier: 66022965.

Structural connectivity in multiple sclerosis and modeling of disconnection.

BACKGROUND: Multiple sclerosis (MS) is characterized by focal white matter damage, and when the brain is modeled as a network, lesions can be treated as disconnection events. OBJECTIVE: To evaluate whether modeling disconnection caused by lesions helps explain motor and cognitive impairment in MS. METHODS: Pathways connecting 116 cortical regions were reconstructed with magnetic resonance imaging (MRI) tractography from diffusion tensors averaged across healthy controls (HCs); maps of pathways were applied to 227 relapse-onset MS patients and 50 HCs to derive structural connectivity. Then, the likelihood of individual connections passing through lesions was used to model disconnection. Patients were grouped according to clinical phenotype (113 relapsing-remitting multiple sclerosis (RRMS), 69 secondary progressive multiple sclerosis (SPMS), 45 benign MS), and then network metrics were compared between groups (analysis of variance (ANOVA)) and correlated with motor and cognitive scores (linear regression). RESULTS: Global metrics differentiated RRMS from SPMS and benign MS patients, but not benign from SPMS patients. Nodal connectivity strength replicated global results. After disconnection, few nodes were significantly different between benign MS and RRMS patients. Correlations revealed nodes pertinent to motor and cognitive dysfunctions; these became slightly stronger after disconnection. CONCLUSION: Connectivity did not change greatly after modeled disconnection, suggesting that the brain network is robust against damage caused by MS lesions.

Aortic stiffness in aortic stenosis assessed by cardiovascular MRI: a comparison between bicuspid and tricuspid valves.

OBJECTIVES: To compare aortic size and stiffness parameters on MRI between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with aortic stenosis (AS). METHODS: MRI was performed in 174 patients with asymptomatic moderate-severe AS (mean AVAI 0.57 ± 0.14 cm2/m2) and 23 controls on 3T scanners. Valve morphology was available/analysable in 169 patients: 63 BAV (41 type-I, 22 type-II) and 106 TAV. Aortic cross-sectional areas were measured at the level of the pulmonary artery bifurcation. The ascending and descending aorta (AA, DA) distensibility, and pulse wave velocity (PWV) around the aortic arch were calculated. RESULTS: The AA and DA areas were lower in the controls, with no difference in DA distensibility or PWV, but slightly lower AA distensibility than in the patient group. With increasing age, there was a decrease in distensibility and an increase in PWV. After correcting for age, the AA maximum cross-sectional area was higher in bicuspid vs. tricuspid patients (12.97 [11.10, 15.59] vs. 10.06 [8.57, 12.04] cm2, p < 0.001), but there were no significant differences in AA distensibility (p = 0.099), DA distensibility (p = 0.498) or PWV (p = 0.235). Patients with BAV type-II valves demonstrated a significantly higher AA distensibility and lower PWV compared to type-I, despite a trend towards higher AA area. CONCLUSIONS: In patients with significant AS, BAV patients do not have increased aortic stiffness compared to those with TAV despite increased ascending aortic dimensions. Those with type-II BAV have less aortic stiffness despite greater dimensions. These results demonstrate a dissociation between aortic dilatation and stiffness and suggest that altered flow patterns may play a role. KEY POINTS: • Both cellular abnormalities secondary to genetic differences and abnormal flow patterns have been implicated in the pathophysiology of aortic dilatation and increased vascular complications associated with bicuspid aortic valves (BAV). • We demonstrate an increased ascending aortic size in patients with BAV and moderate to severe AS compared to TAV and controls, but no difference in aortic stiffness parameters, therefore suggesting a dissociation between dilatation and stiffness. • Sub-group analysis showed greater aortic size but lower stiffness parameters in those with BAV type-II AS compared to BAV type-I.

Perioperative Cerebral Microbleeds After Adult Cardiac Surgery.

Background and Purpose- Cerebral microbleeds (CMBs) have been observed using magnetic resonance imaging in patients with cardiovascular risk factors, cognitive deterioration, small vessel disease, and dementia. They are a well-known consequence of cerebral amyloid angiopathy, chronic hypertension, and diffuse axonal injury, among other causes. However, the frequency and location of new CMBs postadult cardiac surgery, in association with cognition and perioperative risk factors, have yet to be studied. Methods- Pre- and postsurgery magnetic resonance susceptibility-weighted images and neuropsychological tests were analyzed from a total of 75 patients undergoing cardiac surgery (70 men; mean age, 63±10 years). CMBs were identified by a neuroradiologist blinded to clinical details who independently assessed the presence and location of CMBs using standardized criteria. Results- New CMBs were identified in 76% of patients after cardiac surgery. The majority of new CMBs were located in the frontal lobe (46%) followed by the parietal lobe (15%), cerebellum (13%), occipital lobe (12%), and temporal lobe (8%). Patients with new CMBs typically began with a higher prevalence of preexisting CMBs ( P=0.02). New CMBs were associated with longer cardiopulmonary bypass times ( P=0.003), and there was a borderline association with lower percentage hematocrit ( P=0.04). Logistic regression analysis suggested a ≈2% increase in the odds of acquiring new CMBs during cardiac surgery for every minute of bypass time (odds ratio, 1.02; 95% CI, 1.00-1.05; P=0.04). Postoperative neuropsychological decline was observed in 44% of patients and seemed to be unrelated to new CMBs. Conclusions- New CMBs identified using susceptibility-weighted images were found in 76% of patients who underwent cardiac surgery. CMBs were globally distributed with the highest numbers in the frontal and parietal lobes. Our regression analysis indicated that length of cardiopulmonary bypass time and lowered hematocrit may be significant predictors for new CMBs after cardiac surgery. Clinical Trial Registration- URL: http://www.isrctn.com . Unique identifier: 66022965.

Measurement of Whole-Brain and Gray Matter Atrophy in Multiple Sclerosis: Assessment with MR Imaging.

Purpose To compare available methods for whole-brain and gray matter (GM) atrophy estimation in multiple sclerosis (MS) in terms of repeatability (same magnetic resonance [MR] imaging unit) and reproducibility (different system/field strength) for their potential clinical applications. Materials and Methods The softwares ANTs-v1.9, CIVET-v2.1, FSL-SIENAX/SIENA-5.0.1, Icometrix-MSmetrix-1.7, and SPM-v12 were compared. This retrospective study, performed between March 2015 and March 2017, collected data from (a) eight simulated MR images and longitudinal data (2 weeks) from 10 healthy control subjects to assess the cross-sectional and longitudinal accuracy of atrophy measures, (b) test-retest MR images in 29 patients with MS acquired within the same day at different imaging unit field strengths/manufacturers to evaluate precision, and (c) longitudinal data (1 year) in 24 patients with MS for the agreement between methods. Tissue segmentation, image registration, and white matter (WM) lesion filling were also evaluated. Multiple paired t tests were used for comparisons. Results High values of accuracy (0.87-0.97) for whole-brain and GM volumes were found, with the lowest values for MSmetrix. ANTs showed the lowest mean error (0.02%) for whole-brain atrophy in healthy control subjects, with a coefficient of variation of 0.5%. SPM showed the smallest mean error (0.07%) and coefficient of variation (0.08%) for GM atrophy. Globally, good repeatability (P > .05) but poor reproducibility (P < .05) were found for all methods. WM lesion filling technique mainly affected ANTs, MSmetrix, and SPM results (P < .05). Conclusion From this comparison, it would be possible to select a software for atrophy measurement, depending on the requirements of the application (research center, clinical trial) and its goal (accuracy and repeatability or reproducibility). An improved reproducibility is required for clinical application. © RSNA, 2018 Online supplemental material is available for this article.

Sedentary Time and MRI-Derived Measures of Adiposity in Active Versus Inactive Individuals.

OBJECTIVE: The aim of this study was to examine cross-sectional associations between objectively measured sedentary time and magnetic resonance imaging (MRI)-assessed adiposity in a population at high risk for type 2 diabetes (T2DM) and to determine whether associations are modified by the recommended levels of moderate-to-vigorous physical activity (MVPA). METHODS: Sedentary time and MVPA were measured objectively by using accelerometers. Linear regression models examined the association of sedentary time with liver, visceral, subcutaneous, and total abdominal fat (quantified by using MRI). Interaction terms determined whether results were consistent across activity categories (active [> 150 min/wk of MVPA] vs. inactive [< 150 min/wk of MVPA]). RESULTS: One hundred and twenty-four participants (age = 64.0 ± 7.1 years; male = 65.3%; BMI = 31.8 ± 5.6 kg/m2 ) were included. Following adjustment, each 60 minutes of sedentary time was associated with 1.74 L higher total abdominal fat, 0.62 L higher visceral fat, 1.14 L higher subcutaneous fat, and 1.86% higher liver fat. When results were stratified by MVPA (active vs. inactive), sedentary time was associated with greater liver, visceral, and total abdominal fat in the inactive group only. CONCLUSIONS: These findings suggest that sedentary time is associated with higher levels of inter- and intraorgan fat, but associations with liver, visceral, and total abdominal fat were stronger in those who do not reach the current exercise recommendations for health.

Brain MRI atrophy quantification in MS: From methods to clinical application.

Patients with the main clinical phenotypes of multiple sclerosis (MS) manifest varying degrees of brain atrophy beyond that of normal aging. Assessment of atrophy helps to distinguish clinically and cognitively deteriorating patients and predicts those who will have a less-favorable clinical outcome over the long term. Atrophy can be measured from brain MRI scans, and many technological improvements have been made over the last few years. Several software tools, with differing requirements on technical ability and levels of operator intervention, are currently available and have already been applied in research or clinical trial settings. Despite this, the measurement of atrophy in routine clinical practice remains an unmet need. After a short summary of the pathologic substrates of brain atrophy in MS, this review attempts to guide the clinician towards a better understanding of the methods currently used for quantifying brain atrophy in this condition. Important physiologic factors that affect brain volume measures are also considered. Finally, the most recent research on brain atrophy in MS is summarized, including whole brain and various compartments thereof (i.e., white matter, gray matter, selected CNS structures). Current methods provide sufficient precision for cohort studies, but are not adequate for confidently assessing changes in individual patients over the scale of months or a few years.

Estimating Brain Lesion Volume Change in Multiple Sclerosis by Subtraction of Magnetic Resonance Images.

BACKGROUND: Change in lesion volume over time, measured on brain magnetic resonance imaging (MRI) scans, is an important outcome measure for natural history studies and clinical trials in multiple sclerosis (MS). PURPOSE: To develop and test image analysis methods for quantification of lesion volume change in order to improve reliability. METHODS: The technique is based on registration and subtraction, and was evaluated in a cohort of 20 MS patients with dual-echo images acquired annually over a period of four years. The study protocol was approved by the local ethics review boards of participating centers, and all subjects gave written informed consent. The repeatability was compared to that obtained by the standard method for obtaining lesion volume change by evaluating the total volume at each time point, and then subtracting the volumes to obtain the difference. RESULTS: Compared to the standard method, the subtraction method had improved intrarater correlation (0.95 and 0.72 for the subtraction method and the standard method, respectively) and interrater correlation (0.51 and 0.28, respectively). Furthermore, the mean time required to analyze the scans from one patient was 41 minutes for the subtraction method compared to 125 minutes for the standard method. CONCLUSION: Use of the subtraction algorithm leads to improved reliability and lower operator fatigue in clinical trials and studies of the natural history of MS.

Dynamic cerebral autoregulation following acute ischaemic stroke: Comparison of transcranial Doppler and magnetic resonance imaging techniques.

Novel MRI-based dynamic cerebral autoregulation (dCA) assessment enables the estimation of both global and spatially discriminated autoregulation index values. Before exploring this technique for the evaluation of focal dCA in acute ischaemic stroke (AIS) patients, it is necessary to compare global dCA estimates made using both TCD and MRI. Both techniques were used to study 11 AIS patients within 48 h of symptom onset, and nine healthy controls. dCA was assessed by the rate of return of CBFV (Rturn) following a sudden drop induced by the thigh cuff manoeuvre. No significant between-hemisphere differences were seen in controls using either the TCD or MRI technique. Inter-hemisphere averaged Rturn values were not different between TCD (1.89 ± 0.67%/s) and MRI (2.07 ± 0.60%/s) either. In patients, there were no differences between the affected and unaffected hemispheres whether assessed by TCD (Rturn 0.67 ± 0.72 vs. 0.98 ± 1.09%/s) or MRI (0.55 ± 1.51 vs. 1.63 ± 0.63%/s). Rturn for both TCD and MRI was impaired in AIS patients compared to controls in both unaffected and affected hemispheres (ANOVA, p = 0.00005). These findings pave the way for wider use of MRI for dCA assessment in health and disease.

Characterisation of cardiomyopathy by cardiac and aortic magnetic resonance in patients new to hemodialysis.

OBJECTIVES: Cardiomyopathy is a key factor in accelerated cardiovascular mortality in haemodialysis (HD) patients. We aimed to phenotype cardiac and vascular dysfunction by tagged cardiovascular magnetic resonance (CMR) imaging in patients recently commencing HD. METHODS: Fifty-four HD patients and 29 age and sex-matched controls without kidney disease were studied. Left ventricular (LV) mass, volumes, ejection fraction (EF), concentric remodelling, peak-systolic circumferential strain (PSS), peak diastolic strain rate (PDSR), LV dyssynchrony, aortic distensibility and aortic pulse wave velocity were determined. RESULTS: Global systolic function was reduced (EF 51 ± 10%, HD versus 59 ± 5%, controls, p < 0.001; PSS 15.9 ± 3.7% versus 19.5 ± 3.3%, p < 0.001). Diastolic function was decreased (PDSR 1.07 ± 0.33s(-1) versus 1.31 ± 0.38s(-1), p = 0.003). LV mass index was increased (63[54,79]g/m(2) versus 46[42,53]g/m(2), p < 0.001). Anteroseptal reductions in PSS were apparent. These abnormalities remained prevalent in the subset of HD patients with preserved EF >50% (n = 35) and the subset of HD patients without diabetes (n = 40). LV dyssynchrony was inversely correlated to diastolic function, EF and aortic distensibility. Diastolic function was inversely correlated to LV dyssynchrony, concentric remodelling, age and aortic pulse wave velocity. CONCLUSION: Patients new to HD have multiple cardiac and aortic abnormalities as characterised by tagged CMR. Cardio-protective interventions are required from initiation of therapy. KEY POINTS: • First characterisation of cardiomyopathy by tagged CMR in haemodialysis patients. • Diastolic function was correlated to LV dyssynchrony, concentric remodelling and aortic PWV. • Reductions in strain localised to the septal and anterior wall. • Bioimpedance measures were unrelated to LV strain, suggesting volume-independent pathogenetic mechanisms. • Multiple abnormalities persisted in the HD patient subset with preserved EF or without diabetes.

T1- vs. T2-based MRI measures of spinal cord volume in healthy subjects and patients with multiple sclerosis.

BACKGROUND: The reliable and efficient measurement of spinal cord atrophy is of growing interest in monitoring disease progression in multiple sclerosis (MS). METHODS: We compared T1- and T2-weighted MRI for measuring cervical spinal cord volume in 31 patients with MS and 18 age-matched controls (NC) from T1-weighted gradient recalled echo and T2-weighted fast spin-echo 1.5 T axial acquisitions. The two sequences were matched on slice thickness, signal averages and voxel size. An active surface software tool determined the normalized mean cervical cord cross-sectional area. RESULTS: T1-derived cord areas were higher than T2 areas in the whole cohort (estimated mean difference = 7.03 mm(2) (8.89%); 95% Confidence Interval (CI): 5.91, 8.14; p < 0.0001) and in both groups separately. There were trends for lower spinal cord areas in MS vs. NC with both sequences. For the T1 cord area, the mean difference was 3.7 mm(2) (4.55%) (95% CI: -1.36, 8.78; p = 0.15). For the T2 cord area, the difference was larger [mean difference 4.9 mm(2) (6.52%) (95% CI: -0.83, 10.67); p = 0.091]. The T1 and T2 cord areas showed similar weak to moderate correlations with measures of clinical status and T2 spinal cord lesion volume in the MS group. Superficial spinal cord T2 lesions had no apparent confounding effect on the outlining tool. The mean intra-rater and inter-rater coefficients of variation ranged from 0.27 to 0.91% for T1- and 0.66 to 0.99% for T2-derived cord areas. CONCLUSION: T2-weighted images may prove efficient for measuring cervical spinal cord atrophy in MS, with the added advantage of lesion detectability.

A longitudinal MRI study of cervical cord atrophy in multiple sclerosis.

There is an urgent need of fast and accurate methods for the longitudinal quantification of cervical cord atrophy in multiple sclerosis (MS). Aim of this study was to compare a new semi-automatic method [the active surface (AS) method] with an existing cord segmentation method (the Losseff method) to measure cervical cord atrophy progression in MS patients. Using the AS and Losseff methods, normalized cervical cord cross-sectional area (CSA) was compared between 35 MS patients and 9 healthy controls (HC) at baseline and after 2.3 years of follow-up. Correlations with clinical/conventional MRI variables and a power calculation study were also performed. At follow-up, the Losseff method detected a 1 % CSA increase in HC and a 3.5 % decrease in MS patients (p = 0.01), while the AS method detected a 0.1 % decrease in HC and 3 % decrease in MS patients (p = 0.02). The AS method was more sensitive to associations with disability/conventional MRI variables and also provided lower numbers of subjects per arm compared to the Losseff method in a putative clinical trial scenario. Cord AS CSA measurements were more sensitive to longitudinal changes in MS patients than Losseff measurements. Cord AS CSA might be a valuable surrogate outcome measure for monitoring neuroprotection in MS.

Comparison of semi-automated methods to quantify infarct size and area at risk by cardiovascular magnetic resonance imaging at 1.5T and 3.0T field strengths.

BACKGROUND: There is currently no gold standard technique for quantifying infarct size (IS) and ischaemic area-at-risk (AAR [oedema]) on late gadolinium enhancement imaging (LGE) and T2-weighted short tau inversion recovery imaging (T2w-STIR) respectively. This study aimed to compare the accuracy and reproducibility of IS and AAR quantification on LGE and T2w-STIR imaging using Otsu's Automated Technique (OAT) with currently used methods at 1.5T and 3.0T post acute ST-segment elevation myocardial infarction (STEMI). METHODS: Ten patients were assessed at 1.5T and 10 at 3.0T. IS was assessed on LGE using 5-8 standard-deviation thresholding (5-8SD), full-width half-maximum (FWHM) quantification and OAT. AAR was assessed on T2w-STIR using 2SD and OAT. Accuracy was assessed by comparison with manual quantification. Interobserver and intraobserver variabilities were assessed using Intraclass Correlation Coefficients and Bland-Altman analysis. IS using each technique was correlated with left ventricular ejection fraction (LVEF). RESULTS: FWHM and 8SD-derived IS closely correlated with manual assessment at both field strengths (1.5T: 18.3 ± 10.7% LV Mass [LVM] with FWHM, 17.7 ± 14.4% LVM with 8SD, 16.5 ± 10.3% LVM with manual quantification; 3.0T: 10.8 ± 8.2% LVM with FWHM, 11.4 ± 9.0% LVM with 8SD, 11.5 ± 9.0% LVM with manual quantification). 5SD and OAT overestimated IS at both field strengths. OAT, 2SD and manually quantified AAR closely correlated at 1.5T, but OAT overestimated AAR compared with manual assessment at 3.0T. IS and AAR derived by FWHM and OAT respectively had better reproducibility compared with manual and SD-based quantification. FWHM IS correlated strongest with LVEF. CONCLUSIONS: FWHM quantification of IS is accurate, reproducible and correlates strongly with LVEF, whereas 5SD and OAT overestimate IS. OAT accurately assesses AAR at 1.5T and with excellent reproducibility. OAT overestimated AAR at 3.0T and thus cannot be recommended as the preferred method for AAR quantification at 3.0T.

Size distribution of air bubbles entering the brain during cardiac surgery.

BACKGROUND: Thousands of air bubbles enter the cerebral circulation during cardiac surgery, but whether high numbers of bubbles explain post-operative cognitive decline is currently controversial. This study estimates the size distribution of air bubbles and volume of air entering the cerebral arteries intra-operatively based on analysis of transcranial Doppler ultrasound data. METHODS: Transcranial Doppler ultrasound recordings from ten patients undergoing heart surgery were analysed for the presence of embolic signals. The backscattered intensity of each embolic signal was modelled based on ultrasound scattering theory to provide an estimate of bubble diameter. The impact of showers of bubbles on cerebral blood-flow was then investigated using patient-specific Monte-Carlo simulations to model the accumulation and clearance of bubbles within a model vasculature. RESULTS: Analysis of Doppler ultrasound recordings revealed a minimum of 371 and maximum of 6476 bubbles entering the middle cerebral artery territories during surgery. This was estimated to correspond to a total volume of air ranging between 0.003 and 0.12 mL. Based on analysis of a total of 18667 embolic signals, the median diameter of bubbles entering the cerebral arteries was 33 µm (IQR: 18 to 69 µm). Although bubble diameters ranged from ~5 µm to 3.5 mm, the majority (85%) were less than 100 µm. Numerous small bubbles detected during cardiopulmonary bypass were estimated by Monte-Carlo simulation to be benign. However, during weaning from bypass, showers containing large macro-bubbles were observed, which were estimated to transiently affect up to 2.2% of arterioles. CONCLUSIONS: Detailed analysis of Doppler ultrasound data can be used to provide an estimate of bubble diameter, total volume of air, and the likely impact of embolic showers on cerebral blood flow. Although bubbles are alarmingly numerous during surgery, our simulations suggest that the majority of bubbles are too small to be harmful.

Impact of perioperative infarcts after cardiac surgery.

BACKGROUND AND PURPOSE: Brain injury after cardiac surgery is a serious concern for patients and their families. The purpose of this study was to use 3-T fluid attenuated inversion recovery MRI to characterize new and preexisting cerebral ischemic lesions in patients undergoing cardiac surgery and to test whether the accumulation of new ischemic lesions adversely affects cognition. METHODS: Digital comparison of before and after fluid attenuated inversion recovery MRI images was performed for 77 cardiac surgery patients. The burden of preexisting versus new ischemic lesions was quantified and compared with the results of baseline and postoperative neuropsychological testing. RESULTS: After surgery, new lesions were identified in 31% of patients, averaging 0.5 lesions per patient (67 mm(3) [0.004%] of brain tissue). Patients with preexisting lesions were 10× more likely to receive new lesions after surgery than patients without preexisting lesions. Preexisting ischemic lesions were observed in 64% of patients, averaging 19.4 lesions (1542 mm(3) [0.1%] of brain tissue). New lesions in the left hemisphere were significantly smaller and more numerous (29 lesions; median volume, 44 mm(3); volume range, 5-404 mm(3)) than those on the right (10 lesions; median volume, 128 mm(3); volume range, 13-1383 mm(3)), which is consistent with a cardioembolic source of particulate emboli. Overall, the incidence of postoperative cognitive decline was 46% and was independent of whether new lesions were present. CONCLUSIONS: New lesions after cardiac surgery added a small (≈4%) contribution to the burden of preexisting cerebrovascular disease and did not seem to affect cognitive function. CLINICAL TRIAL REGISTRATION URL: http://public.ukcrn.org.uk. Unique identifier: UKCRN ID: 11702.

Myocardial T1 and extracellular volume fraction measurement in asymptomatic patients with aortic stenosis: reproducibility and comparison with age-matched controls.

AIMS: (i) To establish the test-retest reproducibility of myocardial T1 and extracellular volume (ECV) fraction measurement in asymptomatic patients with moderate-severe aortic stenosis (AS), (ii) to compare reproducibility using motion-corrected (MOCO) parametric T1 maps for analysis vs. full MOLLI series of images, and (iii) to compare T1 and ECV between patients and age-matched controls. METHODS AND RESULTS: 3 T cardiac MRI was performed twice on 10 patients (median interval 7 days) to assess reproducibility. An additional 40 patients and 22 asymptomatic controls underwent a single MRI. Native T1 and ECV were calculated by outlining the myocardium on T1 maps generated inline, and using an offline T1 fit on the MOCO multiple inversion-time raw image series, in the reproducibility cohort (n = 10). Reproducibility was excellent using the inline T1 maps (CoVs for T1: 1.77%; ECV: 6.52%) and good using the full MOLLI series (CoVs for T1: 8.52%; ECV: 12.98%). On comparing AS and controls, who were well matched for age, gender and co-morbidities, there was no significant difference in the native T1 or ECV (T1 = 1103.32 ± 33.07 vs. 1092.27 ± 34.29; ECV = 0.243 ± 0.019 vs. 0.251 ± 0.026 in patients and controls, P > 0.05), which was maintained even after splitting the patients into moderate and severe AS subgroups. CONCLUSION: The test-retest reproducibility of myocardial T1 quantification using MOLLI is excellent in patients with AS and is highest using inline generated T1 maps for analysis. There was no difference in native myocardial T1 or ECV between asymptomatic patients with moderate-severe AS and age-matched controls without valve disease.

Associations of Sedentary Time with Fat Distribution in a High-Risk Population.

PURPOSE: The effect of sedentary behavior on regional fat deposition, independent of physical activity, remains equivocal. We examined the cross-sectional associations between objectively measured sedentary time and markers of regional fat distribution (heart, liver, visceral, subcutaneous, and total body fat) in a population at a high risk of type 2 diabetes mellitus (T2DM). METHODS: Participants were recruited from primary care to two diabetes prevention programs. Sedentary time (<25 counts per 15 s) was measured using ActiGraph GT3X accelerometers. Heart, liver, visceral, subcutaneous, and total body fat were quantified using magnetic resonance images. Fat volumes were calculated by multiplying the cross-sectional areas of the fat-containing pixels by the slice thickness. The liver fat percentage was measured using a representative region of interest created in the right lobe of the liver, avoiding the main portal veins. Linear regression models examined the association of sedentary time with markers of regional fat deposition. RESULTS: Sixty-six participants (age, 47.9 ± 16.2 yr; male, 50.0%) were included. After adjustment for several covariates, including glycemia, whole-body fat, and moderate-to-vigorous physical activity, each 30 min of sedentary time was associated with 15.7 cm higher heart fat (P = 0.008), 1.2% higher liver fat (P = 0.026), and 183.7 cm higher visceral fat (P = 0.039). CONCLUSIONS: This study provides new evidence suggesting that objectively measured sedentary behavior may have an independent association with heart, liver, and visceral fat in individuals at a high risk of T2DM.

Intertechnique agreement and interstudy reproducibility of strain and diastolic strain rate at 1.5 and 3 Tesla: a comparison of feature-tracking and tagging in patients with aortic stenosis.

PURPOSE: To determine the interstudy reproducibility of myocardial strain and peak early-diastolic strain rate (PEDSR) measurement on cardiovascular magnetic resonance imaging (MRI) assessed with feature tracking (FT) and tagging, in patients with aortic stenosis (AS). MATERIALS AND METHODS: Cardiac MRI was performed twice (1-14 days apart) in 18 patients (8 at 1.5 Tesla [T], 10 at 3T) with moderate-severe AS. Circumferential peak systolic strain (PSS) and PEDSR were measured in all patients. Longitudinal PSS and PEDSR were assessed using FT in all patients, and tagging in the 3T sub-group. RESULTS: PSS was higher with FT than tagging (21.0 ± 1.9% versus 17.0 ± 3.4% at 1.5T, 21.4 ± 4.0% versus 17.7 ± 3.0% at 3T, P < 0.05), as was PEDSR (1.3 ± 0.3 s(-1) versus 1.0 ± 0.3 s(-1) , P = 0.10 at 1.5T and 1.3 ± 0.4 s(-1) versus 0.8 ± 0.3 s(-1) , P < 0.05 at 3T). The reproducibility of PSS was excellent with FT (coefficient of variation [CoV] 9-10%) and good with tagging at 1.5T (13-19%). Reproducibility of circumferential PEDSR was best at 1.5T when only basal/mid slices were included (CoV 12%), but moderate to poor at 3T (29-35%). Reproducibility of longitudinal strain was good with FT (10-16%) but moderate for PEDSR (∼30%). CONCLUSION: In patients with AS, FT consistently produces higher values compared with tagging. The interstudy reproducibility of PSS is excellent with FT and good with tagging. The reproducibility of circumferential PEDSR at 1.5T is good when only basal and mid slices are used.