Aaron McCann

Comparison of RootMUSIC and Discrete Wavelet Transform Analysis of Doppler Ultrasound Blood Flow Waveforms to Detect Microvascular Abnormalities in Type I Diabetes

The earliest signs of cardiovascular disease occur in microcirculations. Changes to mechanical and structural properties of these small resistive vessels alter the impedance to flow, subsequent reflected waves, and consequently, flow waveform morphology. In this paper, we compare two frequency analysis techniques: 1) rootMUSIC and 2) the discrete wavelet transform (DWT) to extract features of flow velocity waveform morphology captured using Doppler ultrasound from the ophthalmic artery (OA) in 30 controls and 38 age and sex matched Type I diabetics. Conventional techniques for characterizing Doppler velocity waveforms, such as mean velocity, resistive index, and pulsatility index, revealed no significant differences between the groups. However, rootMUSIC and the DWT provided highly correlated results with the spectral con tent in bands 2-7 (30-0.8 Hz) significantly elevated in the diabetic group (p <; 0.05). The spectral distinction between the groups may be attributable to manifestations of underlying pathophysiological processes in vascular impedance and consequent wave reflections, with bands 5 and 7 related to age. Spectral descriptors of OA blood velocity waveforms are better indicators of preclinical microvascular abnormalities in Type I diabetes than conventional measures. Although highly correlated DWT proved slightly more discriminatory than rootMUSIC and has the advantage of extending to subheart rate frequencies, which may be of interest.

Impaired microvascular properties in uncomplicated type 1 diabetes identified by Doppler ultrasound of the ocular circulation.

Objective: Quantification of Doppler flow velocity waveforms has been shown to predict adverse cardiovascular outcomes and identify altered downstream haemodynamics and vascular damage in a number of organ beds. We employed novel techniques to quantify Doppler flow velocity waveforms from the retro bulbar circulation. Methods and results: In total, 39 patients with uncomplicated Type 1 diabetes mellitus, and no other significant cardiovascular risk factors were compared with 30 control subjects. Flow velocity waveforms were captured from the ophthalmic artery (OA), central retinal artery (CRA) and the common carotid artery. The flow velocity profiles were analysed in the time domain to calculate the resistive index (RI), and time-frequency domain using novel discrete wavelet transform methods for comparison. Analysis of flow waveforms from the OA and CRA identified specific frequency band differences between groups, occurring independently of potential haemodynamic or metabolic confounding influences. No changes were identified in the calculated RI from any arterial site. Conclusion: Novel analysis of the arterial flow velocity waveforms recorded from the retro bulbar circulation identified quantifiable differences in Doppler flow velocity waveform morphology in patients with diabetes prior to the development of overt retinopathy. The technique may be useful as an additional marker of cardiovascular risk.

Colour Doppler ultrasound of the ocular circulation in patients with systemic lupus erythematosus identifies altered microcirculatory haemodynamics

We assessed whether quantitative analysis of Doppler flow velocity waveforms is able to identify subclinical microvascular abnormalities in SLE and whether eigenvector analysis can detect changes not detectable using the resistive index (RI). Fifty-four SLE patients with no conventional cardiovascular risk factors, major organ involvement or retinopathy were compared to 32 controls. Flow velocity waveforms were obtained from the ophthalmic artery (OA), central retinal artery (CRA) and common carotid artery (CA). The waveforms were analysed using eigenvector decomposition and compared between groups at each arterial site. The RI was also determined. The RI was comparable between groups. In the OA and CRA, there were significant differences in the lower frequency sinusoidal components (P < 0.05 for each component). No differences were apparent in the CA between groups. Eigenvector analysis of Doppler flow waveforms, recorded in proximity of the terminal vascular bed, identified altered ocular microvascular haemodynamics in SLE. Altered waveform structure could not be identified by changes in RI, the traditional measure of downstream vascular resistance. This analytical approach to waveform analysis is more sensitive in detecting preclinical microvascular abnormalities in SLE. It may hold potential as a useful tool for assessing disease activity, response to treatment, and predicting future vascular complications.

Flow-mediated dilatation of the brachial artery is a poorly reproducible indicator of microvascular function in Type I diabetes mellitus

BACKGROUND Flow-mediated dilatation (FMD) of the brachial artery is commonly measured as a surrogate marker of endothelial function. Its measurement is, however, technically demanding and reports regarding its reproducibility have not always been favourable. AIM Two Type I diabetes and control group comparator studies were conducted to assess the reproducibility of FMD and to analyse blood flow data normally discarded during FMD measurement. DESIGN The studies were sequential and differed only with regard to operator and ultrasound machine. Seventy-two subjects with diabetes and 71 controls were studied in total. METHODS Subjects had FMD measured conventionally. Blood velocity waveforms were averaged over 10 pulses post forearm ischaemia and their component frequencies analysed using the wavelet transform, a mathematical tool for waveform analysis. The component frequencies were grouped into 11 bands to facilitate analysis. RESULTS Subjects were well-matched between studies. In Study 1, FMD was significantly impaired in subjects with Type I diabetes vs. controls (median 4.35%, interquartile range 3.10-4.80 vs. 6.50, 4.79-9.42, P < 0.001). No differences were detected between groups in Study 2, however. However, analysis of blood velocity waveforms yielded significant differences between groups in two frequency bands in each study. CONCLUSION This report highlights concerns over the reproducibility of FMD measures. Further work is required to fully elucidate the role of analysing velocity waveforms after forearm ischaemia.

Root-MUSIC analysis of nitric oxide-mediated changes in ophthalmic artery blood flow velocity waveforms

Clinical and experimental studies indicate that structural and functional changes in the microvasculature can predate or accompany risk factors for cardiovascular disease at the earliest stages in the disease process. In the current work, both simulated and actual Doppler ultrasound maximum blood velocity waveform envelopes recorded from the ophthalmic artery were analysed using a root-MUSIC and least squares fitting approach to determine amplitude frequency spectra. Both amplitude and frequency components of noise contaminated simulated waveforms were reliably determined indicating the robustness of the technique. The technique was then used to compare the spectral content of the ophthalmic artery blood velocity waveforms of normal controls in three test states: at baseline, following administration of GTN, a nitric oxide donor, and following administration of L-Name, a nitric oxide inhibitor. Principal components derived from root-MUSIC analysis discriminated between waveforms in baseline and non-baseline test states (p<0.00001) and between GTN and non-GTN test states (p=0.0002).

Ocular Blood Flow Analysis Detects Microvascular Abnormalities in Impaired Glucose Tolerance

Please cite this paper as: Quinn, Hamilton, McCann, Agnew, Millar, Lockhart, Harbinson and McVeigh (2011). Ocular Blood Flow Analysis Detects Microvascular Abnormalities in Impaired Glucose Tolerance. Microcirculation 18(7), 532–540.

Wavelet Entropy of Doppler Ultrasound Blood Velocity Flow Waveforms Distinguishes Nitric Oxide-Modulated States

Wavelet entropy assesses the degree of order or disorder in signals and presents this complex information in a simple metric. Relative wavelet entropy assesses the similarity between the spectral distributions of two signals, again in a simple metric. Wavelet entropy is therefore potentially a very attractive tool for waveform analysis. The ability of this method to track the effects of pharmacologic modulation of vascular function on Doppler blood velocity waveforms was assessed. Waveforms were captured from ophthalmic arteries of 10 healthy subjects at baseline, after the administration of glyceryl trinitrate (GTN) and after two doses of N(G)-nitro-L-arginine-methyl ester (L-NAME) to produce vasodilation and vasoconstriction, respectively. Wavelet entropy had a tendency to decrease from baseline in response to GTN, but significantly increased after the administration of L-NAME (mean: 1.60 ± 0.07 after 0.25 mg/kg and 1.72 ± 0.13 after 0.5 mg/kg vs. 1.50 ± 0.10 at baseline, p < 0.05). Relative wavelet entropy had a spectral distribution from increasing doses of L-NAME comparable to baseline, 0.07 ± 0.04 and 0.08 ± 0.03, respectively, whereas GTN had the most dissimilar spectral distribution compared with baseline (0.17 ± 0.08, p = 0.002). Wavelet entropy can detect subtle changes in Doppler blood velocity waveform structure in response to nitric-oxide-mediated changes in arteriolar smooth muscle tone.

Epicardial potentials computed from the body surface potential map using inverse electrocardiography and an individualised torso model improve sensitivity for acute myocardial infarction diagnosis

Introduction: Epicardial potentials (EPs) derived from the body surface potential map (BSPM) improve acute myocardial infarction (AMI) diagnosis. In this study, we compared EPs derived from the 80-lead BSPM using a standard thoracic volume conductor model (TVCM) with those derived using a patient-specific torso model (PSTM) based on body mass index (BMI). Methods: Consecutive patients presenting to both the emergency department and pre-hospital coronary care unit between August 2009 and August 2011 with acute ischaemic-type chest pain at rest were enrolled. At first medical contact, 12-lead electrocardiograms and BSPMs were recorded. The BMI for each patient was calculated. Cardiac troponin T (cTnT) was sampled 12 hours after symptom onset. Patients were excluded from analysis if they had any ECG confounders to interpretation of the ST-segment. A cardiologist assessed the 12-lead ECG for ST-segment elevation myocardial infarction by Minnesota criteria and the BSPM. BSPM ST-elevation (STE) was ⩾0.2 mV in anterior, ⩾0.1 mV in lateral, inferior, right ventricular or high right anterior and ⩾0.05 mV in posterior territories. To derive EPs, the BSPM data were interpolated to yield values at 352 nodes of a Dalhousie torso. Using an inverse solution based on the boundary element method, EPs at 98 cardiac nodes positioned within a standard TVCM were derived. The TVCM was then scaled to produce a PSTM using a model developed from computed tomography in 48 patients of varying BMIs, and EPs were recalculated. EPs >0.3 mV defined STE. A cardiologist blinded to both the 12-lead ECG and BSPM interpreted the EP map. AMI was defined as cTnT ⩾0.1 µg/L. Results: Enrolled were 400 patients (age 62 ± 13 years; 57% male); 80 patients had exclusion criteria. Of the remaining 320 patients, the BMI was an average of 27.8 ± 5.6 kg/m2. Of these, 180 (56%) had AMI. Overall, 132 had Minnesota STE on ECG (sensitivity 65%, specificity 89%) and 160 had BSPM STE (sensitivity 81%, specificity 90%). EP STE occurred in 165 patients using TVCM (sensitivity 88%, specificity 95%; p < 0.001) and in 206 patients using PSTM (sensitivity 98%, specificity 79%; p < 0.001). Of those with AMI by cTnT and EPs ⩽0.3 mV using TVCM (n = 22), 18 (82%) patients had EPs >0.3 mV when an individualised PSTM was used. Conclusion: Among patients presenting with ischaemic-type chest pain at rest, EPs derived from BSPM using a novel PSTM significantly improve sensitivity for AMI diagnosis.

Detecting early microvascular disease in type 1 diabetes: wavelet transform analysis of Doppler blood velocity waveforms

Diabetic retinopathy is associated with markedly increased risk of cardiovascular events. Analysis of retrobulbar blood velocity waveforms should help characterise microvessels since waveform morphology is partly determined by wave reflection. This approach could potentially allow the detection of abnormalities earlier than is currently possible. Ultrasound examinations of the common carotid, ophthalmic (OA) and central retinal (CRA) arteries were undertaken on 39 subjects with type 1 diabetes (no retinopathy) and 39 controls. Waveforms were characterised using the discrete wavelet transform, and frequency data categorised into 11 bands. After correcting for possible confounders, in the OA, the mean amplitude was higher for subjects with diabetes in band 4 (p=0.022). In the CRA, the mean amplitude was higher for subjects with diabetes in bands 2 (p=0.012), 3 (p<0.001) and 5 (p=0.028). Abnormalities were most pronounced when signals were captured close to the microvasculature, providing evidence that they may be due to microvascular alterations. Br J Diabetes Vasc Dis 2011;12:40-47

Statin Therapy Does Not Significantly Alter Microvascular Function in Uncomplicated Hypertension

Objective Young patients with uncomplicated hypertension are frequently exempt from statin therapy as they generally fall below current treatment thresholds. This study examined whether there may be evidence of improved microvascular function in young patients with grade 1 hypertension after 12 weeks of statin therapy. Methods This was a randomized double-blind placebo-controlled crossover study in which 42 statin-naïve participants with grade 1 hypertension (mean systolic/diastolic blood pressure 142/92 mmHg) were randomized to receive either simvastatin 40 mg or a placebo for 12 weeks, followed by a 4-week washout period, after which the arms crossed for a further 12 weeks. Measures of vascular function were recorded at the beginning and end of each study period equating to four measures in total. The brachial artery was studied by flow-mediated dilatation (FMD) together with the resistive and pulsatility indices and mean velocity of flow. Results Statin therapy did not significantly alter the change in FMD seen in the brachial artery [standardized differential mean = 0.02 (0.23), confidence interval (CI) = −0.45 to 0.48, p = 0.932]. No significant changes were seen in the brachial artery mean velocity (CI = −9.68 to 11.51, p = 0.861), resistive index (CI = −0.11 to 0.12, p = 0.903), or pulsatility index (CI = −5.82 to 4.91, p = 0.864). Conclusion This study did not demonstrate any significant changes in established measures of microvascular function after treatment with a statin in a young hypertensive population with no antecedent cardiovascular disease. This may indicate that either the intervention was insufficiently vasoactive to produce a clinically detectable improvement in vascular function, or that the means used to assess the microvasculature were insufficiently sensitive to detect what may have been quite minor changes.