Diagnosis Of Small Vessel Disease Research Articles

The role of ultrasound screening in the diagnosis of small vessel disease

The role of ultrasound screening in the diagnosis of small vessel disease

MRI-Compatible Microcirculation System Using Ultrasonic Pumps for Microvascular Imaging on 3T MRI.

The diagnosis of small vessel disease is attracting interest; however, it remains difficult to visualize the microvasculature using 3 Tesla (T) magnetic resonance imaging (MRI). Therefore, this study aimed to visualize the microvascular structure and measure a slow flow on 3T MRI. We developed a microcirculation system using piezoelectric pumps connected to small tubes (0.4, 0.5, 0.8, and 1.0 mm) and evaluated various MR sequences and imaging parameters to identify the most appropriate acquisition parameters. We found that the system could image small structures with a diameter of 0.5 mm or more when using a 1 m-long tube (maximal signal intensity of 241 in 1 mm, 199 in 0.8 mm, and 133 in 0.5 mm). We also found that the highest signal-to-noise ratio (SNR) appeared on 2-dimensional time-of-flight low-resolution imaging and that the flow velocity (10.03 cm/s) was similar to the actual velocity (11.01 cm/s in a flowmeter) when velocity encoding of 30 cm/s was used in a 0.8 mm-diameter tube. In conclusion, this study demonstrates that a microcirculation system can be used to image small vessels. Therefore, our results could serve as a basis for research on vessels’ anatomical structure and pathophysiological function in small vessel disease.

Borderzone Infarction and Small Vessel Disease in a Sample of Egyptian Stroke Patients: Differences and Similarities.

The anatomical location of white matter hyperintense lesions in small vessel disease are apparently similar to those of borderzone infarction. The objective of this study is to find clinical and radiological points of differentiation between the two vascular disorders in a sample of Egyptian patients which might have an impact on primary and secondary prevention. Ischemic stroke patients with white matter lesions were categorized into two groups: small vessel disease and borderzone infarctions. NIHSS was done on admission. Risk factor profile was reported, and investigations done including: HbA1C, lipid profile, CRP, ECG, echocardiography, carotid duplex, brain MRI, MRA and MR perfusion study. 46 patients completed the study, 29 with SVD and 17 with BZI. Smoking, hypertension and recurrent stroke were more common in borderzone infarctions, but only diabetes was significantly higher (p = 0.047). Limb shaking was more observed in borderzone infarctions (p = 0.049). Radiologically: lacunar pattern was observed more in small vessel disease, while rosary pattern was more in borderzone infarctions (p = 0.04). FLAIR symmetrical lesions and microbleeds were more significant in small vessel disease (p = <0.001; 0.048, respectively). Perfusion study time to peak denoted evidence of significant hypoperfusion in all regions of interest in borderzone infarctions. Limb shaking, retinal claudication or syncope, with MRI showing rosary pattern of white matter hyperintensity, few microbleeds and markedly impaired perfusion favor the diagnosis of borderzone infarctions. On the other hand, presence of lacunae, FLAIR showing symmetrical WMH and microbleeds with minimal or no perfusion deficit suggests the diagnosis of small vessel disease.

The cGMP-Degrading Enzyme Phosphodiesterase-5 (PDE5) in Cerebral Small Arteries of Older People.

Cerebral small vessel disease in deep penetrating arteries is a major cause of lacunar infarcts, white matter lesions and vascular cognitive impairment. Local cerebral blood flow in these small vessels is controlled by endothelial-derived nitric oxide, which exerts a primary vasodilator stimulus on vascular myocytes, via cytoplasmic cyclic GMP. Here, we investigated whether the cGMP-degrading enzyme phosphodiesterase-5 (PDE5) is present in small penetrating arteries in the deep subcortical white matter of older people. Frontal cortical tissue blocks were examined from donated brains of older people (n = 42, 24 male: 18 female, median age 81, range: 59-100 years). PDE5, detected by immunohistochemical labeling, was graded as absent, sparse, or abundant in vascular cells within small arteries in subcortical white matter (vessel outer diameter: 20-100 µm). PDE5 labeling within arterial myocytes was detected in all cases. Degree of PDE5 expression (absent, sparse, or abundant) was not associated with age or with neuropathological diagnosis of small vessel disease. In conclusion, PDE5 is present in vascular myocytes within small penetrating arteries in older people. This is a potential molecular target for pharmacological interventions.

Abstract TP194: Albuminuria Predicts Early Neurological Deterioration in Patients with Acute Ischemic Stoke

Background: Chronic kidney disease (CKD), defined as a reduced glomerular filtration rate (GFR) or albuminuria, is associated with an increased risk of cardiovascular events, including stroke. However, the association between CKD and acute-phase stroke has not yet been thoroughly studied. We investigated the impact of estimated GFR (eGFR) and albuminuria on early neurological deterioration (END) in patients with acute ischemic stroke. Methods: In this retrospective study, we enrolled 294 consecutive patients with acute ischemic stroke admitted to our stroke center from January 2011 to September 2012. General blood and urine examinations, including eGFR and urinary albumin/creatinine ratio (UACR), were performed on admission. Other risk factors and comorbidities were also examined. END was defined as a ≥ 2-point increase in the National Institutes of Health Stroke Scale (NIHSS) score within 7 days. Statistical significance between the END and non-END group was assessed using Pearson’s chi-square test for categorical variables. Multiple logistic regression analyses were performed to identify predictors of END. Results: END was observed in 60 patients (20.4%). Age (P = 0.003), admission Blood glucose level (P = 0.036), large vessel disease (P = 0.022), small vessel disease (P &lt; 0.001), UACR (P &lt; 0.001), and admission NIHSS score (P &lt; 0.001) were significantly associated with END, but no relationship between eGFR and END was found. The optimal cutoff level, sensitivity, and specificity of UACR levels to distinguish the END group from the non-END group were 39.6 mg/g creatinine, 83.3 and 52.1%, respectively. On multivariable logistic regression analysis showed that END was positively associated with high UACR (≥ 39.6 mg/g creatinine; odds ratio [OR], 3.36; 95% confidence interval [CI], 1.60-7.51; P = 0.0011) and high admission NIHSS score(≥ 6 points, OR, 2.27; 95% CI, 1.11-4.78; P = 0.0245), and negatively associated with diagnosis of small vessel disease (OR, 0.11; 95% CI, 0.0054-0.80; P = 0.0277). Conclusions: Our data suggest that high UACR on admission may predict early neurological deterioration in patients with acute ischemic stroke. Larger prospective studies are further required to clarify the correlation between albuminuria and END.

Low Serum n-3 Polyunsaturated Fatty Acid/n-6 Polyunsaturated Fatty Acid Ratio Predicts Neurological Deterioration in Japanese Patients with Acute Ischemic Stroke

Background: Epidemiological and clinical trials have shown that n-3 polyunsaturated fatty acids (PUFAs) reduce the incidence of coronary heart disease or stroke. However, the association between PUFAs and acute-phase stroke has not yet been thoroughly studied. We investigated the impact of serum PUFAs on early neurological deterioration (END) in patients with acute ischemic stroke. Methods: In this retrospective study, we enrolled 281 Japanese patients (mean age: 75 ± 13 years; 165 males) with acute ischemic stroke diagnosed within 24 h of onset. General blood examinations, including PUFAs (n-3 PUFAs: eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA, and n-6 PUFAs: arachidonic acid, AA), were performed on admission. Other risk factors and comorbidities were also examined. END was defined as a ≥2-point increase in the National Institutes of Health Stroke Scale (NIHSS) score within a 72-hour period. Statistical significance between the END and non-END group was assessed using Wilcoxon rank sum tests or Student's t tests for categorical variables. Multiple logistic regression analyses were performed to identify predictors of END. Results: END was observed in 75 patients (26.7%). Diabetes mellitus (p = 0.003), high-sensitivity C-reactive protein (hs-CRP) level (p < 0.001), prior stroke (p = 0.035), ischemic heart disease (p = 0.029), EPA/AA ratio (p = 0.003), DHA/AA ratio (p = 0.002), EPA+DHA/AA ratio (p = 0.002), diagnosis of small vessel disease (p = 0.004) and admission NIHSS score (p < 0.001) were significantly associated with END. We used separate multiple logistic regression analyses for the EPA/AA, DHA/AA and EPA+DHA/AA ratios, because EPA and DHA are considered covariant factors (r = 0.544; p < 0.0001). Multiple logistic regression analyses showed that END was positively associated with diabetes mellitus, hs-CRP level and NIHSS score on admission, and negatively associated with the EPA/AA ratio (odds ratio, OR: 0.18; 95% confidence interval, CI: 0.05-0.58; p = 0.003), DHA/AA ratio (OR: 0.045; 95% CI: 0.006-0.30; p = 0.001), EPA+DHA/AA ratio (OR: 0.45; 95% CI: 0.26-0.74; p = 0.002) and diagnosis of small vessel disease. Conclusions: Our data suggest that a low serum n-3 PUFA/n-6 PUFA ratio on admission may predict neurological deterioration in Japanese patients with acute ischemic stroke. Large-scale prospective studies are further required to clarify the role of PUFAs in the acute phase of ischemic stroke.

Anatomical Variations in the Posterior Part of the Circle of Willis and Vascular Pathology in Bilateral Thalamic Infarction

Bilateral paramedian thalamic infarction is a rare subtype of stroke the etiology of which still remains undetermined in many patients. From a computed tomography (CT)/magnetic resonance imaging report database, we identified and analyzed 48 patients with bilateral paramedian thalamic infarction on diffusion-weighted imaging. Vascular pathologies were noted on CT angiography (CTA)/magnetic resonance angiography (MRA) and the P1 segments of the posterior cerebral artery (PCA) described as normal, hypoplastic, or absent. Vascular imaging revealed top of the basilar artery (BA) occlusion in 6 (12.5%), BA occlusion in 4 (8.3%), BA stenosis in 1 (2.1%), and BA hypoplasia in 3 (6.3%), PCA occlusion in 4 (8.3%), and PCA stenosis in 4 (8.3%) patients. In 18 (37.5%) patients, one or both P1 segments of the PCA were hypoplastic or absent. Patients with hypoplastic/absent P1 segments were more likely to have exclusively bilateral paramedian thalamic lesions (P < .001). An embolic source could be identified in 25 (55.6%) patients; there were no significant differences between both groups. Vascular imaging is useful to determine underlying vascular pathologies and may support the diagnosis of small vessel disease in those patients with isolated bilateral paramedian thalamic infarction, hypoplastic/absent P1 segment of the PCA, and lack of vascular pathology.

Relationship between angiographic graft vessel disease and microvascular reaction after heart transplantation

This study tests the correlation of coronary angiographic findings with the extent of microvascular reaction in right ventricular endomyocardial biopsies (EMBs) in transplanted hearts. In EMBs (n = 209) of 30 heart transplant patients (8 female, 22 male, mean age 48 years) microvascular reaction, i.e. endothelial cell swelling and vascular wall thickening (both grade 0-2), was graded by light microscopy at ×200. Patients' first and last coronary angiography (CA) (mean time after heart transplantation [HTx] 8 and 44 months) were graded according to the Stanford Classification and the presence of diameter irregularities was evaluated semi-quantitatively. We found a correlation of angiographic type B lesions with endothelial cell swelling during the first 5 months and vascular wall thickening during the fifth to fourteenth month after HTx (p <0.05). In patients with diameter irregularities and type B1 lesions in their first CA and type C lesions in their last CA, there was pronounced endothelial cell swelling in the early postoperative period (p <0.05). There was a tendency towards an increased vascular wall thickening in these patients during the later postoperative period. Graft vessel disease affects large and small coronary arteries and capillaries. Small vessel disease is characterized by architectural changes in blood vessel walls. Serial investigations of EMBs for diagnosis of small vessel disease complement the present diagnostic tools.

Small-vessel disease relates to poor poststroke survival in a 12-year follow-up

We sought to compare ultra-long-term poststroke survival in small-vessel disease (SVD) vs non-SVD subtype of stroke. We followed patients hospitalized with acute ischemic stroke (age 55-85) for 12 years. The diagnosis of SVD was based on the criteria of Trial of Org 10172 in Acute Stroke Treatment. A detailed medical history regarding the relevant risk factors was obtained. Stroke severity was assessed with the modified Rankin Scale (mRS) at 3 months. Influence of the SVD subtype of stroke was analyzed using Kaplan-Meier log-rank analysis with endpoint all-cause death, and Cox regression proportional hazards model was constructed for multivariate analysis. The association between SVD and causes of death (cardiac, brain-related, all other) was analyzed using Kaplan-Meier log-rank analysis. Of the 486 patients, stroke etiology was SVD in 63 patients (13.0%). Median survival was 4.3 years for SVD and 7.9 years for non-SVD (p ≤ 0.001). In the stepwise Cox regression analysis adjusted for relevant confounders, independent predictors of death were SVD (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.06-2.41), advanced age (HR 1.07, 95% CI 1.05-1.09), stroke severity (mRS 3-5 vs 1-2; HR 2.02, 95% CI 1.58-2.58), smoking (HR 1.44, 95% CI 1.10-1.88), and cardiac failure (HR 1.53, 95% CI 1.14-2.06). SVD was associated with cardiac cause of death (p = 0.021). In this well-characterized ischemic stroke cohort of patients aged 55-85 years with a 12-year follow-up, acute index stroke attributable to SVD was associated with poorer long-term survival and higher risk for cardiac death than other stroke subtypes.

Early Clinical Diagnosis of Lacunar Strokes

To the Editor: Phillips and colleagues1 report the GAIN Americas data to describe the relationships between the OCSP2 and TOAST3 classifications tools, focusing on the accuracy of the OCSP classification in the early diagnosis of a lacunar stroke. The authors classify lacunar syndromes (LS) within 6 hours of stroke onset and conclude that the OCSP classification is highly accurate in detecting a lacunar stroke. As reference standard they used the diagnosis of small-vessel disease according to the TOAST classification performed at 7 days after stroke onset or at hospital discharge, after a battery of investigations which was not …

34.23 Significance of quantification of myocardial blood flow by cardiac PET in diabetic patients for the diagnosis of small vessel disease

34.23 Significance of quantification of myocardial blood flow by cardiac PET in diabetic patients for the diagnosis of small vessel disease

Relationship between angiographic graft vessel disease and microvascular reaction after heart transplantation

This study tests the correlation of coronary angiographic findings with the extent of microvascular reaction in right ventricular endomyocardial biopsies (EMBs) in transplanted hearts. In EMBs (n = 209) of 30 heart transplant patients (8 female, 22 male, mean age 48 years) microvascular reaction, i.e. endothelial cell swelling and vascular wall thickening (both grade 0-2), was graded by light microscopy at ×200. Patients' first and last coronary angiography (CA) (mean time after heart transplantation [HTx] 8 and 44 months) were graded according to the Stanford Classification and the presence of diameter irregularities was evaluated semi-quantitatively. We found a correlation of angiographic type B lesions with endothelial cell swelling during the first 5 months and vascular wall thickening during the fifth to fourteenth month after HTx (p <0.05). In patients with diameter irregularities and type B1 lesions in their first CA and type C lesions in their last CA, there was pronounced endothelial cell swelling in the early postoperative period (p <0.05). There was a tendency towards an increased vascular wall thickening in these patients during the later postoperative period. Graft vessel disease affects large and small coronary arteries and capillaries. Small vessel disease is characterized by architectural changes in blood vessel walls. Serial investigations of EMBs for diagnosis of small vessel disease complement the present diagnostic tools.

Cerebral arteriovenous transit time (cTT): a sonographic assessment of cerebral microcirculation using ultrasound contrast agents

:— Transcranial color-coded sonography (TCCS) has been used to investigate major brain-supplying arteries, draining veins and brain parenchyma. Here, we describe a contrast-enhanced TCCS analysis of cerebral arteriovenous transit time (cTT) as a measure of cerebral microcirculation. We evaluate its reproducibility and its correlation with clinical impairment of brain function and neuropsychological tests. A total of 27 patients with cerebral microangiopathy and 30 healthy controls were examined. CTT is defined by the time an ultrasound contrast agent requires to pass from the P2-segment of the posterior cerebral artery to the vein of Galen. This was measured by comparison of power Doppler intensity in two off-line defined regions of interest. Serial intraindividual cTT measurements within several min showed a good reproducibility of this parameter. cTT was significantly longer in patients with cerebral microangiopathy than in controls (Mann–Whitney U test, p < 0.001) and related to cognitive impairment measured by the Mini-Mental-State examination. We conclude that it is a quick and reliable parameter related to increased vascular resistance of the microcirculation or a rarefaction of microvessels. Further studies are needed to show the sensitivity and specificity of cTT in the diagnosis of small vessel disease and the interference of important circulation factors, such as heart failure or blood viscosity.

Endomyocardial biopsy diagnosis of small vessel disease: a clinicopathologic study

We reviewed the clinical history of 191 patients undergoing endomyocardial biopsy and correlated signs and symptoms of heart disease with the presence or absence of small vessel disease. Idiopathic congestive heart failure (78%), arrhythmia (35%), and chest pain (25%) were the most frequent indications for biopsy. Small vessel disease was noted in 61% of the biopsies (67% female, 56% male): 10% severe, 36% moderate, and 15% mild small vessel disease. Patients with hypertension were twice as likely to have small vessel disease than those without hypertension. Of the 27 females with hypertension, 85% had small vessel disease, 67% with either severe or moderate small vessel disease. Small vessel disease was almost twice as frequent in patients with chest pain compared to patients without chest pain. Chest pain was significantly more common in patients with severe small vessel disease than in those with normal small vessels. Of all patients with chest pain, 18% had severe small vessel disease; however, of 20 patients with severe small vessel disease, 45% had chest pain. This analysis suggests that small vessel disease seen in endomyocardial biopsy is more common in women and is related to hypertension. When severe, it is likely to be associated with atypical chest pain.