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1.  Vertebrobasilar ectasia in patients with lacunar stroke: The SPS3 trial 
The clinical implications of vertebrobasilar ectasia (VBE) in patients with cerebral small artery disease are not well defined. We investigated whether VBE is associated with recurrent stroke, major hemorrhage, and death in a large cohort of patients with recent lacunar stroke.
Materials and methods
Maximum diameters of the vertebral and basilar arteries were measured by magnetic resonance angiography and computed tomographic angiography in 2621 participants in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial. VBE was defined a priori as basilar artery >4.5 mm and/or vertebral artery >4.0 mm. Patient characteristics and risks of stroke recurrence and mortality during follow-up (median 3.5 years) were compared between patients with and without VBE.
VBE affecting ≥1 artery was present in 200 (7.6%) patients. Patient features independently associated with VBE were increasing age, male sex, white race-ethnicity, hypertension, and higher baseline diastolic blood pressure. Baseline systolic blood pressure was inversely associated with VBE. After adjustment for other risk factors, VBE was not predictive of recurrent stroke (HR 1.3, 95% CI 0.85-1.9) or major hemorrhage (HR 1.5, CI 0.94-2.6), but was of death (HR 1.7, CI 1.1-2.7).
In this large well-characterized cohort of patients with recent lacunar stroke, VBE was predictive of death, but not recurrent stroke or major hemorrhage. In these exploratory analyses, the frequency of VBE was directly related to diastolic blood pressure but inversely related to systolic blood pressure.
PMCID: PMC4408219  PMID: 25817614
lacunar stroke; prognosis; recurrent stroke; small vessel disease; death; arterial diameter; vertebrobasilar ectasia
2.  Clinical Correlates of Infarct Shape and Volume in Lacunar Strokes The SPS3 Trial 
Background and Purpose
Infarct size and location are thought to correlate with different mechanisms of lacunar infarcts. We examined the relationship between the size and shape of lacunar infarcts and vascular risk factors and outcomes.
We studied 1679 participants in the Secondary Prevention of Small Subcortical Stroke trial with a lacunar infarct visualized on DWI. Infarct volume was measured planimetrically, and shape was classified based on visual analysis after 3D reconstruction of axial MRI slices.
Infarct shape was ovoid/spheroid in 63%, slab 12%, stick 7%, and multi- component 17%. Median infarct volume was smallest in ovoid/spheroid relative to other shapes: 0.46, 0.65, 0.54, and 0.90 ml respectively, p< 0.001. Distributions of vascular risk factors were similar across the four groups except that patients in the ovoid/spheroid and stick groups were more often diabetic and those with multi-component had significantly higher blood pressure at study entry. Intracranial stenosis did not differ among groups (p=0.2). Infarct volume was not associated with vascular risk factors. Increased volume was associated with worse functional status at baseline and 3 months. Overall, 162 recurrent strokes occurred over an average of 3.4 years of follow-up with no difference in recurrent ischemic stroke rate by shape or volume.
In patients with recent lacunar stroke, vascular risk factor profile was similar amongst the different infarct shapes and sizes. Infarct size correlated with worse short- term functional outcome. Neither shape nor volume was predictive of stroke recurrence.
PMCID: PMC4198938  PMID: 25190442
Small subcortical infarcts; Lacunar infarcts; Infarct shape; Infarct size; Diffusion weighted imaging; Lacunar stroke
3.  Lacunar strokes in patients with diabetes: Risk factors, infarct location, and prognosis: The SPS3 Study 
Background and Purpose
Diabetes is an independent risk factor for lacunar strokes. Few data are available regarding patient features, infarct location, and recurrent vascular events for diabetic patients with lacunar stroke.
We compared features at study entry and prognosis during 3.6 years of follow-up of diabetic vs. non-diabetic patients with recent lacunar stroke participating in the Secondary Prevention of Small Subcortical Strokes (SPS3) randomized trial.
Among the 3020 participants, the prevalence of diabetes was 37% with a mean duration of 11 years. Diabetes was independently associated with slightly younger age (63 years vs. 64 years, p<0·001), Hispanic ethnicity (36% vs. 28%, p<0·0001), ischemic heart disease (11% vs. 6%, p=0·002), and peripheral vascular disease (5% vs. 2%, p<0·001). Diabetic patients more frequently had intracranial stenosis ≥50% (p<0·001), infarcts involving the brainstem or cerebellum (p<0·001), and more extensive white matter abnormalities (p<0·001). Diabetic patients were almost twice as likely to have a recurrent stroke (HR 1·8; 95% CI 1·4–2·3), recurrent ischemic stroke (HR 1·8; 95% CI 1·4–2·4), disabling/fatal stroke (HR 1·8; 95% CI 1·2–2·9), myocardial infarction (HR 1·7; 95% CI 1·0–2·8) and death (HR 2·1 (95% CI 1·6–2·8) compared with non-diabetics.
Diabetic patients with lacunar stroke have a distinctive clinical profile that includes double the prevalence of systemic and intracranial atherosclerosis, preferential involvement of the posterior circulation, and a poor prognosis for recurrent stroke and death.
PMCID: PMC4146755  PMID: 25034716
stroke; diabetes; lacunar stroke; small artery disease
4.  The Secondary Prevention of Small Subcortical Strokes (SPS3) study 
Small subcortical strokes, also known as lacunar strokes, comprise more than 25% of brain infarcts, and the underlying vasculopathy is the most common cause of vascular cognitive impairment. How to optimally prevent stroke recurrence and cognitive decline in S3 patients is unclear. The aim of the Secondary Prevention of Small Subcortical Strokes study (Trial registration: NCT00059306) is to define strategies for reducing stroke recurrence, cognitive decline, and major vascular events.
Secondary Prevention of Small Subcortical Strokes is a randomised, multicentre clinical trial (n = 3000) being conducted in seven countries, and sponsored by the US NINDS/NIH. Patients with symptomatic small subcortical strokes in the six-months before and an eligible lesion on magnetic resonance imaging are simultaneously randomised, in a 2 × 2 factorial design, to antiplatelet therapy – 325 mg aspirin daily plus 75 mg clopidogrel daily, vs. 325 mg aspirin daily plus placebo, double-blind – and to one of two levels of systolic blood pressure targets –‘intensive’ (<130 mmHg) vs. ‘usual’ (130–149 mmHg). Participants are followed for an average of four-years. Time to recurrent stroke (ischaemic or haemorrhagic) is the primary outcome and will be analysed separately for each intervention. The secondary outcomes are the rate of cognitive decline and major vascular events. The primary and most secondary outcomes are adjudicated centrally by those unaware of treatment assignment.
Secondary Prevention of Small Subcortical Strokes will address several important clinical and scientific questions by testing two interventions in patients with recent magnetic resonance imaging-defined lacunar infarcts, which are likely due to small vessel disease. The results will inform the management of millions of patients with this common vascular disorder.
PMCID: PMC4214141  PMID: 21371282
antiplatelet therapy; hypertension; lacunar stroke; randomised clinical trial; SPS3
5.  Introduction of non-linear elasticity models for characterization of shape and deformation statistics: application to contractility assessment of isolated adult cardiocytes 
BMC Biophysics  2011;4:17.
We are exploring the viability of a novel approach to cardiocyte contractility assessment based on biomechanical properties of the cardiac cells, energy conservation principles, and information content measures. We define our measure of cell contraction as being the distance between the shapes of the contracting cell, assessed by the minimum total energy of the domain deformation (warping) of one cell shape into another. To guarantee a meaningful vis-à-vis correspondence between the two shapes, we employ both a data fidelity term and a regularization term. The data fidelity term is based on nonlinear features of the shapes while the regularization term enforces the compatibility between the shape deformations and that of a hyper-elastic material.
We tested the proposed approach by assessing the contractile responses in isolated adult rat cardiocytes and contrasted these measurements against two different methods for contractility assessment in the literature. Our results show good qualitative and quantitative agreements with these methods as far as frequency, pacing, and overall behavior of the contractions are concerned.
We hypothesize that the proposed methodology, once appropriately developed and customized, can provide a framework for computational cardiac cell biomechanics that can be used to integrate both theory and experiment. For example, besides giving a good assessment of contractile response of the cardiocyte, since the excitation process of the cell is a closed system, this methodology can be employed in an attempt to infer statistically significant model parameters for the constitutive equations of the cardiocytes.
PMCID: PMC3201040  PMID: 21854653
6.  Image Processing Techniques for Assessing Contractility in Isolated Neonatal Cardiac Myocytes 
We describe a computational framework for the quantitative assessment of contractile responses of isolated neonatal cardiac myocytes. To the best of our knowledge, this is the first report on a practical and accessible method for the assessment of contractility in neonatal cardiocytes. The proposed methodology is comprised of digital video recording of the contracting cell, signal preparation, representation by polar Fourier descriptors, and contractility assessment. The different processing stages are variants of mathematically sound and computationally robust algorithms very well established in the scientific community. The described computational approach provides a comprehensive assessment of the neonatal cardiac myocyte contraction without the need of elaborate instrumentation. The versatility of the methodology allows it to be employed in determining myocyte contractility almost simultaneously with the acquisition of the Ca2+ transient and other correlates of cell contraction. The proposed methodology can be utilized to evaluate changes in contractile behavior resulting from drug intervention, disease models, transgeneity, or other common applications of neonatal cardiocytes.
PMCID: PMC3151489  PMID: 21826135
7.  Image Processing Techniques for Assessing Contractility in Isolated Adult Cardiac Myocytes 
We describe a computational framework for the comprehensive assessment of contractile responses of enzymatically dissociated adult cardiac myocytes. The proposed methodology comprises the following stages: digital video recording of the contracting cell, edge preserving total variation-based image smoothing, segmentation of the smoothed images, contour extraction from the segmented images, shape representation by Fourier descriptors, and contractility assessment. The different stages are variants of mathematically sound and computationally robust algorithms very well established in the image processing community. The physiologic application of the methodology is evaluated by assessing overall contraction in enzymatically dissociated adult rat cardiocytes. Our results demonstrate the effectiveness of the proposed approach in characterizing the true, two-dimensional, “shortening” in the contraction process of adult cardiocytes. We compare the performance of the proposed method to that of a popular edge detection system in the literature. The proposed method not only provides a more comprehensive assessment of the myocyte contraction process but also can potentially eliminate historical concerns and sources of errors caused by myocyte rotation or translation during contraction. Furthermore, the versatility of the image processing techniques makes the method suitable for determining myocyte shortening in cells that usually bend or move during contraction. The proposed method can be utilized to evaluate changes in contractile behavior resulting from drug intervention, disease modeling, transgeneity, or other common applications to mammalian cardiocytes.
PMCID: PMC2829623  PMID: 20224633

Results 1-7 (7)