Crispian Oates

Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria

Aims/hypothesisType 1 diabetes is associated with premature arterial disease. Bone-marrow derived, circulating endothelial progenitor cells (EPCs) are believed to contribute to endothelial repair. The hypothesis tested was that circulating EPCs are reduced in young people with type 1 diabetes without vascular injury and that this is associated with impaired endothelial function and increased carotid intima–media thickness (CIMT).MethodsWe compared 74 people with type 1 diabetes with 80 healthy controls. CD34, CD133, vascular endothelial (VE) growth factor receptor-2 (VEGFR-2) and VE-cadherin antibodies were used to quantify EPCs and progenitor cell subtypes using flow-cytometry. Ultrasound assessment of endothelial function by brachial artery flow-mediated dilatation (FMD) and CIMT was made. Circulating endothelial markers, inflammatory markers and plasma plasminogen activator inhibitor-1 (PAI-1) levels were measured.ResultsCD34+VE-cadherin+, CD133+VE-cadherin+ and CD133+VEGFR-2+ EPC counts were significantly lower in people with diabetes (46–69%; p = 0.004–0.043). In people with type 1 diabetes, FMD was reduced by 45% (p < 0.001) and CIMT increased by 25% (p < 0.001), these being correlated (r = −0.25, p = 0.033). There was a significant relationship between FMD and CD34+VE-cadherin+ (r = 0.39, p = 0.001), CD133+VEGFR-2+ (r = 0.25, p = 0.037) and CD34+ (r = 0.34, p = 0.003) counts. Circulating high-sensitivity C-reactive protein, PAI-1, interleukin-6 and E-selectin were significantly higher in the diabetes group (p < 0.001 to p = 0.049), the last two of these correlating with FMD (r = −0.27, p = 0.028 and r = −0.24, p = 0.048, respectively).Conclusions/interpretationThese findings suggest that abnormalities of endothelial function in addition to pro-inflammatory and pro-thrombotic states are already common in people with type 1 diabetes before development of clinically evident arterial damage. Low EPC counts confirm risk of macrovascular complications and may account for impaired endothelial function and predict future cardiovascular events.

Photoplethysmography detection of lower limb peripheral arterial occlusive disease: a comparison of pulse timing, amplitude and shape characteristics

The assessment and diagnosis of lower limb peripheral arterial occlusive disease (PAOD) is important since it can lead progressively to disabling claudication, ischaemic rest pain and gangrene. Historically, the first assessment has been palpation of the peripheral pulse since it can become damped, delayed and diminished with disease. In this study we investigated the clinical value of objective photoplethysmography (PPG) pulse measurements collected simultaneously from the right and left great toes to diagnose disease in the lower limbs. In total, 63 healthy subjects and 44 patients with suspected lower limb disease were studied. Pulse wave analysis techniques extracted timing, amplitude and shape characteristics for both toes and for right-to-left toe differences. Normative ranges of pulse characteristics were then calculated for the healthy subject group. The relative diagnostic values of the different pulse features for detecting lower limb arterial disease were determined, referenced to the established ankle-brachial pressure index (ABPI) measurement. The ranges of pulse characteristics and degree of bilateral similarity in healthy subjects were established, and the degrees of pulse delay, amplitude reduction, and damping and bilateral asymmetry were quantified for different grades of disease. When pulse timing, amplitude and shape features were ranked in order of diagnostic performance, the shape index (SI) gave substantial agreement with ABPI (>90% accuracy, kappa 0.75). SI also detected higher grade disease, for legs with an ABPI less than 0.5, with a sensitivity of 100%. The simple-to-calculate timing differences between pulse peaks produced a diagnostic accuracy of 88% for all grades of arterial disease (kappa 0.70), and 93% for higher grade disease (kappa 0.77). These contrasted with the limited discriminatory value of PPG pulse amplitude. The low-cost and simplicity of this optical-based technology could offer significant benefits to healthcare, such as in primary care where non-invasive, accurate and simple-to-use (de-skilled) diagnostic techniques are desirable.

Comparison of Lower Limb Arterial Assessments Using Color-Duplex Ultrasound and Ankle/Brachial Pressure Index Measurements

The strength of agreement between two noninvasive methods of assessing lower limb arterial disease and their relationship to patient symptoms following exercise have been investigated. Color-duplex ultrasound (CDU) and ankle/brachial pressure index (ABPI) (before and after exercise) measurements were obtained from 200 consecutive patients referred to a vascular investigations laboratory. From these patients, 290 limbs were available for study, comprising limbs without previous vascular surgery, from patients without diabetes and who could attempt a walking exercise test. The overall level of agreement between CDU and resting ABPI measurements was 83% (Kappa 0.66). The ABPI technique identified the more serious disease; a resting ABPI of less than 0.6 gave 100% agreement with CDU. With higher resting ABPIs the level of agreement became poorer: 83% (0.6 ≤ ABPI < 0.9) and 76% (normal ABPI ≥ 0.9). The addition of postexercise ABPI measurements in determining significant arterial disease increased the (continued on next page) (Abstract continued) strength of relationship between the two techniques by only 2% (85%, Kappa 0.69). The exercise test was generally limited by the most symptomatic limb in each patient, and the agreement between CDU and postexercise ABPI measurements in these limbs was higher at 93% (Kappa 0.81). In comparison, agreement for the least symptomatic group of limbs was found to be poor (69%, Kappa 0.37). Compared with symptoms after exercise, overall agreements with CDU and ABPI were both 67% (Kappa 0.27). The agreement was better (91%) when the resting ABPI was less than 0.6. The ABPI is biased toward the detection of more severe disease and is more consistent with CDU when the most symptomatic limbs are compared. The relationship between either test and symptoms after exercise is strong only for limbs with major disease.

Thermography and colour duplex ultrasound assessments of arterio-venous fistula function in renal patients.

Vascular and clinical assessments of arterio-venous fistula (AVF) function and access are important in patients undergoing or preparing to undergo renal dialysis. Objective assessment techniques include colour duplex ultrasound and more recently medical infrared thermography. Ideally, these should help assess problems relating to fistula failure or to vascular steal from the hand which can result from excessive fistula blood flow. The clinical value of thermography, as yet, has not been assessed for this patient group. The aims of this study were therefore to investigate the relationships between thermography skin temperature measurement and (a) quantitative ultrasound measurement of AVF blood flow, and (b) qualitative clinical assessment of vascular steal from the hands. Fifteen adult patients underwent thermal imaging of the upper limbs, colour duplex ultrasound to derive AVF blood flow from brachial artery blood flow measurements, and a clinical evaluation for vascular steal. Temperature measurements were extracted from the thermograms, including bilateral arm and hand (Fistula -- Non-Fistula) differences, for comparison with derived AVF blood flow and steal grading. Derived AVF blood flow ranged from 30 to 1,950 ml min(-1), with a mean rate close to one litre per minute. Thermography detected the warmer superficial veins in proximity to the patent fistulas, with bilateral differences in fistula region skin temperature correlated with derived AVF blood flow (using maximum temperature measurements the correlation was +0.71 [p < 0.01]; and using mean temperature measurements the correlation was +0.56 [p < 0.05]). When thermography measurements were compared with the clinical assessment of steal the mean hand temperature differences separated steal from non-steal patients with an accuracy of greater than 90%. In summary, we have now demonstrated the potential clinical value of medical infrared thermography for assessing AVF function in renal patients.

Beyond the ankle-brachial pressure index for the diagnosis of peripheral arterial disease--time for a new look at photoplethysmography.

Peripheral arterial disease (PAD) is common, affecting about 20% of people over 60 years. The PAD confers a high cardiovascular risk and there is a need for an easy test to confirm its presence in the primary care so that appropriate specialist referral can be made. For many years, the ankle-brachial pressure index (ABPI) has been available as a first-line quantitative assessment of PAD. However, it has been unpopular due to concerns about its repeatability in a nonspecialist setting. In this issue, Ro et al describe a comparison continuous wave (CW) Doppler ultrasound with ABPI and photoplethysmography (PPG) in the detection of stenotic peripheral disease. They show that the sensitivity of ABPI is poor particularly in diagnosing the disease in the tibial segment and that an improvement in sensitivity is gained by performing CW Doppler together with ABPI and PPG. The ABPI has previously been shown to have good sensitivity and specificity compared to angiographic imaging. It is also readily available in the community in primary care with lowcost equipment. However, 2 important factors affect the quality of ABPI results. The first is the presence of calcified vessels seen in patients with diabetes, renal disease, and some elderly patients. This leads to underestimation of arterial disease through falsely high readings, as the calcified vessels are relatively incompressible. This can usually be recognized by a high ABPI score of >1.3. The second factor is the need to perform the test to a high standard using a clear protocol. Often, the failure to get reliable results has been due to poor training and performance of the test by relatively inexperienced health care professionals in primary care. The PPG is a low-cost, quick, and simple to do optical technique, but it is however seldom used in routine clinical assessments, largely because of a lack of normal reference ranges, uncertainties due to beat-to-beat variability in pulse characteristics and poorly applied quantitative analysis leading to subjective waveform interpretation. Allen and coworkers have employed systematic pulse wave analysis techniques to show that PPG at the great toe site has good sensitivity and specificity for PAD when compared to the ABPI reference. They provided evidence that normalized pulse shape and its deformity with disease ranks high as an accurate marker for the disease, followed closely second by exploiting bilateral timing differences between the toes. To achieve such confidence in the diagnostic performance of PPG for PAD detection, it has been established that beat-to-beat averaging of the pulse features was essential. Before other techniques for quantifying PAD are introduced there needs to be consideration of the sensitivity and specificity of the technique, ease of use, and the cost and training required to achieve reliable results. The question of training community carers is particularly pertinent, where the technique relies on interpreting waveform shapes rather than performing a protocol that gives a set of numbers that can be recorded. This would be the case with Doppler waveform and PPG techniques as described by Ro et al. Unless there is a very clear-cut distinction between significant and nonsignificant disease, the reliability and reproducibility are likely to be poor. In the case of Doppler waveform analysis, the cost, portability of equipment, and time taken to perform the measurements probably make this modality more suited to a referral center where a full duplex ultrasound can be performed giving both anatomical and hemodynamic information. The key factor in any screening technique is that all disease that warrants further assessment is picked up while recognizing those who clearly do not have significant disease, to avoid unnecessary referral. This implies a test with reasonable sensitivity and high specificity, so that those who definitely do not have disease are not referred unnecessarily. When performed outside a specialist center, it also implies a test that can be reliably performed by a range

Speed of sound and density of ethanol-water mixture across the temperature range 10 to 50 degrees Celsius

Properties such as the speed of sound and density of ethanol-water mixtures are of concern in applications such as the calibration of ultrasound imaging machines, and the study of molecular interactions in binary solutions. The speed of sound and density in ethanol-water mixtures up to a concentration of 40% (w/w) were measured across the temperature range 10 to 50 °C using an ultrasound resonator and a densitometer, with accuracies of ±0.25 m/s and ±0.05 kg/m3 respectively. Measured data were interpolated and presented in forms of multi-polynomial functions of the concentration and the temperature. The functions may serve as a database for reference and also a source to derive parameters such as the temperature coefficient of the speed, the thermal expansion coefficient, and the isentropic compressibility of the mixture, which are commonly used in physiochemical and molecular acoustics studies.

Characterization of the Ultrasound Beam Produced by the MIST Therapy, Wound Healing System

The MIST Therapy wound healing device (Celleration, Eden Prairie, MN, USA), which uses low-frequency ultrasound to deliver an atomized saline spray to acute wounds, was evaluated in a laboratory environment. The output of the MIST device was characterized by its frequency, transmission in the presence and absence of the saline spray and intensity. When measured up to 500 mm away from the transducer tip, the transmission of 39.5 kHz ultrasound was not significantly attenuated by the saline itself. In the absence of the saline spray, the acoustic intensity range of the MIST device was calculated to be 429-188 mW cm(-2) across the manufacturer-specified treatment range (12.5-20 mm). Because of the acoustic impedance mismatch between air and soft tissue, the MIST Therapy device would deliver only 0.1% of this incident intensity into the wound site.

Color Doppler Ultrasound Imaging in the Assessment of Iliac Endofibrosis

Endofibrosis (EF) of the iliac arteries is a flow-limiting condition typically seen in highly trained endurance athletes. Thirty-seven athletes (74 limbs) were referred to our department with suspected EF. All patients had a pre- and postexercise color Doppler ultrasound (CDU) of the iliac arteries. Doppler waveform and peak systolic velocity (PSV) and end-diastolic velocity (EDV) were assessed pre- and postexercise. Endofibrosis was diagnosed with CDU in 24 athletes (29 limbs). Arterial wall and course abnormalities were detected at rest in 20 (67%) symptomatic limbs of athletes with and 4 (22%) symptomatic limbs of athletes without EF. Postexercise abnormal waveforms of the stenotic/damped type were seen in the iliac arteries in all 29 limbs of athletes diagnosed with EF. These waveform changes were accompanied by high PSV (>350 cm/s) and EDV (>150 cm/s), with (n = 10; 34%) or without (n = 19; 66%) the evidence of reduced arterial lumen caliber. Color Doppler ultrasound can be used to detect EF.

Helping expectant mothers understand inadequate ultrasound images

Background Obstetric ultrasound scans may fail to provide all the information that is needed because of poor visualisation. Two main causes of poor visualisation are addressed. These are poor foetal position and poor quality imaging due to beam distortion by overlying fatty tissue. Method To improve communication with patients attending obstetric scans, a poster and leaflet were designed to explain these causes of inadequate scans. A questionnaire was used to assess the value of the poster. Results 57/66 (86%) questionnaires were completed. 52 (91%) found the information on the poster was helpful and well explained. For 8 (14%) the information changed their thoughts about the scan. Conclusion Clear communication aids the expectant mothers understanding of why scans may be suboptimal. The way this is recorded in the scan results is discussed.

Reviewing the curriculum for physics and technology in postgraduate sonography courses.

Physics and technology is seen as a difficult subject by those training in medical ultrasound. The reasons for this are discussed. Who should teach the subject and what should be included are considered. Ways to approach the subject so as to make it more relevant and easier to learn are proposed and a basic syllabus is suggested in an appendix.