Ultrasound entropy may be a new non-invasive measure of pre-clinical vascular damage in young hypertensive patients.

BACKGROUND: The identification of pre-clinical microvascular damage in hypertension by non-invasive techniques has proved frustrating for clinicians. This proof of concept study investigated whether entropy, a novel summary measure for characterizing blood velocity waveforms, is altered in participants with hypertension and may therefore be useful in risk stratification. METHODS: Doppler ultrasound waveforms were obtained from the carotid and retrobulbar circulation in 42 participants with uncomplicated grade 1 hypertension (mean systolic/diastolic blood pressure (BP) 142/92 mmHg), and 26 healthy controls (mean systolic/diastolic BP 116/69 mmHg). Mean wavelet entropy was derived from flow-velocity data and compared with traditional haemodynamic measures of microvascular function, namely the resistive and pulsatility indices. RESULTS: Entropy, was significantly higher in control participants in the central retinal artery (CRA) (differential mean 0.11 (standard error 0.05 cms(-1)), CI 0.009 to 0.219, p 0.017) and ophthalmic artery (0.12 (0.05), CI 0.004 to 0.215, p 0.04). In comparison, the resistive index (0.12 (0.05), CI 0.005 to 0.226, p 0.029) and pulsatility index (0.96 (0.38), CI 0.19 to 1.72, p 0.015) showed significant differences between groups in the CRA alone. Regression analysis indicated that entropy was significantly influenced by age and systolic blood pressure (r values 0.4-0.6). None of the measures were significantly altered in the larger conduit vessel. CONCLUSION: This is the first application of entropy to human blood velocity waveform analysis and shows that this new technique has the ability to discriminate health from early hypertensive disease, thereby promoting the early identification of cardiovascular disease in a young hypertensive population. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov, NCT01047423.

An objective measure of response on whole-body MRI in metastatic hormone sensitive prostate cancer treated with androgen deprivation therapy, external beam radiotherapy, and radium-223.

OBJECTIVES: The aim of this study was to generate an objective method to describe MRI data to assess response in the vertebrae of patients with metastatic hormone sensitive prostate cancer (mHSPC), treated with external beam radiation therapy and systemic therapy with Radium-223 and to correlate changes with clinical outcomes. METHODS: Three sets of whole-body MRI (WBMRI) images were utilized from 25 patients from the neo-adjuvant Androgen Deprivation Therapy pelvic Radiotherapy and RADium-223 (ADRRAD) clinical trial: MRI1 (up to 28 days before Radium-223), MRI2, and MRI3 (2 and 6 months post completion of Radium-223). Radiological response was assessed based on post baseline MRI images. Vertebrae were semi-automatically contoured in the sagittal T1-weighted (T1w) acquisitions, MRI intensity was measured, and spinal cord was used to normalize the measurements. The relationship between MRI intensity vs time to biochemical progression and radiology response was investigated. Survival curves were generated and splitting measures for survival and biochemical progression investigated. RESULTS: Using a splitting measure of 1.8, MRI1 was found to be a reliable quantitative indicator correlating with overall survival (P = 0.023) and biochemical progression (P = 0.014). MRI (3-1) and MRI (3-2) were found to be significant indicators for patients characterized by progressive/non-progressive disease (P = 0.021, P = 0.004) and biochemical progression within/after 12 months (P = 0.007, P = 0.001). CONCLUSIONS: We have identified a potentially useful objective measure of response on WBMRI of vertebrae containing bone metastases in mHSPC which correlates with survival/progression (prognostic) and radiology response (predictive). ADVANCES IN KNOWLEDGE: Measurements of T1w WBMRI normalized intensity may allow identifying potentially useful response biomarkers correlating with survival, radiological response and biochemical progression.

Using a ring to locate femoral head centre in total hip arthroplasty.

AIMS: Traditional methods of determining femoral head centre (FHC) during total hip arthroplasty (THA) rely on measuring the distance from a fixed point on the femur or using a calliper. The aim of this experiment was to investigate how accurately a simple circular ring could locate FHC. METHODS: 144 consecutively available femoral heads (FHs) were collected from patients undergoing THA. Each FH was orientated and mounted on a Sawbone, to create a model of its position on a proximal femur. The ring was applied to the posterior aspect of the FH and a head-centre pin (HCP) was then drilled into the FH and the ring removed, leaving the HCP in place.Each FH was then photographed normal to the axis of the HCP. A MATLAB analysis program then assessed the accuracy of the ring in locating FHC. RESULTS: Mean location accuracy for FHC was 1.77 (range 0.07-5.83) mm with 97.2% within 4 mm and all but 1 within 5 mm. CONCLUSIONS: This ring device located FHC to within 4 mm in 97% of a series of osteoarthritic FHs. This indicates that the posterior aspect of the FH maintains its sphericity late into the osteoarthritic process. Having a simple FHC location device during THA would be of value to control leg length and offset when using the posterior approach.

Ocular blood flow analysis detects microvascular abnormalities in impaired glucose tolerance.

OBJECTIVE: Waveform analysis has been used to assess vascular resistance and predict cardiovascular events. We aimed to identify microvascular abnormalities in patients with IGT using ocular waveform analysis. The effects of pioglitazone were also assessed. METHODS: Forty patients with IGT and 24 controls were studied. Doppler velocity recordings were obtained from the central retinal, ophthalmic, and common carotid arteries, and sampled at 200 Hz. A discrete wavelet-based analysis method was employed to quantify waveforms. The RI was also determined. Patients with IGT were randomized to pioglitazone or placebo, and measurements were repeated after 12-week treatment. RESULTS: In the ocular waveforms, significant differences in power spectra were observed in frequency band 4 (corresponding to frequencies between 6.25 and 12.50 Hz) between groups (p < 0.05). No differences in RI occurred. No association was observed between waveform parameters and fasting glucose or insulin resistance. Pioglitazone had no effect on waveform structure, despite significantly reducing insulin resistance, fasting glucose, and triglycerides (p < 0.05). CONCLUSIONS: Analysis of ocular Doppler flow waveforms using the discrete wavelet transform identified microvascular abnormalities that were not apparent using RI. Pioglitazone improved glucose, insulin sensitivity, and triglycerides without influencing the contour of the waveforms.

Impaired flow-mediated dilatation response in uncomplicated Type 1 diabetes mellitus: influence of shear stress and microvascular reactivity.

Impaired FMD (flow-mediated dilatation) has traditionally been recognized as an indirect marker of NO bioactivity, occurring in disease states such as DM (diabetes mellitus). Endothelium-dependent FMD is a homoeostatic response to short-term increases in local shear stress. Microvascular dysfunction in DM influences blood flow velocity patterns. We explored the determinants of the FMD response in relation to evoked DSS (diastolic shear stress) and forearm microcirculation haemodynamics by quantifying changes in Doppler flow velocity waveforms between groups. Forty patients with uncomplicated Type 1 DM and 32 controls underwent B-mode and Doppler ultrasound scanning to interrogate the brachial artery. Postischaemic Doppler velocity spectral envelopes were recorded and a wavelet-based time-frequency spectral analysis method was employed to track change in distal microcirculatory haemodynamics. No difference in baseline brachial artery diameter was evident between the groups (4.15 compared with 3.94 mm, P=0.23). FMD was significantly impaired in patients with Type 1 DM (3.95 compared with 7.75%, P<0.001). Endothelium-independent dilatation in response to GTN (glyceryl trinitrate) was also significantly impaired (12.07 compared with 18.77%, P<0.001). DSS (dyn/cm2) was significantly reduced in the patient group (mean 20.19 compared with 29.5, P=0.001). Wavelet interrogation of postischaemic flow velocity waveforms identified significant differences between groups. In conclusion, DSS, microcirculatory function and endothelium-independent vasodilatation in response to GTN are important determinants that impact on the magnitude of FMD response and are impaired in patients with Type 1 DM. Impaired FMD response is multifactorial in origin and cannot be attributed solely to a diminished NO bioavailability.

Clinical quantitative MRI and the need for metrology.

MRI has been an essential diagnostic tool in healthcare for several decades. It offers unique insights into most tissues without the need for ionising radiation. Historically, MRI has been predominantly used qualitatively, images are formed to allow visual discrimination of tissues types and pathologies, rather than providing quantitative measurements. Increasingly, quantitative MRI (qMRI) is also finding clinical application, where images provide the basis for physical measurements of, e.g. tissue volume measures and represent aspects of tissue composition and microstructure. This article reviews some common current research and clinical applications of qMRI from the perspective of measurement science. qMRI not only offers additional information for radiologists, but also the opportunity for improved harmonisation and calibration between scanners and as such it is well-suited to large-scale investigations such as clinical trials and longitudinal studies. Realising these benefits, however, presents a new kind of technical challenge to MRI practioners. When measuring a parameter quantitatively, it is crucial that the reliability and reproducibility of the technique are well understood. Strictly speaking, a numerical result of a measurement is meaningless unless it is accompanied by a description of the associated measurement uncertainty. It is therefore necessary to produce not just estimates of physical properties in a quantitative image, but also their associated uncertainties. As the process of determining a physical property from the raw MR signal is complicated and multistep, estimation of uncertainty is challenging and there are many aspects of the MRI process that require validation. With the clinical implementation of qMRI techniques and its continued expansion, there is a clear and urgent need for metrology in this field.

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.

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.

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.