Microwave Radiometry for the Diagnosis and Monitoring of Inflammatory Arthritis.

The ability of microwave radiometry (MWR) to detect with high accuracy in-depth temperature changes in human tissues is under investigation in various medical fields. The need for non-invasive, easily accessible imaging biomarkers for the diagnosis and monitoring of inflammatory arthritis provides the background for this application in order to detect the local temperature increase due to the inflammatory process by placing the appropriate MWR sensor on the skin over the joint. Indeed, a number of studies reviewed herein have reported interesting results, suggesting that MWR is useful for the differential diagnosis of arthritis as well as for the assessment of clinical and subclinical inflammation at the individual large or small joint level and the patient level. MWR showed higher agreement with musculoskeletal ultrasound, used as a reference, than with clinical examination in rheumatoid arthritis (RA), while it also appeared useful for the assessment of back pain and sacroiliitis. Further studies with a larger number of patients are warranted to confirm these findings, taking into account the current limitations of the available MWR devices. This may lead to the production of easily accessible and inexpensive MWR devices that will provide a powerful impetus for personalized medicine.

Joint microwave radiometry for inflammatory arthritis assessment.

OBJECTIVES: Increased in-depth joint temperature measured by the rapid, easy-to-perform microwave radiometry (MWR) method may reflect inflammation, even in the absence of clinical signs. We hypothesized that MWR is useful for RA and spondyloarthritis patients' assessment. METHODS: Clinical examination, joint ultrasound and/or MRI and MWR were performed in two independent patient-control cohorts (n = 243). RESULTS: Among single RA joints MWR performed best in the knee using ultrasound as reference, with 75% sensitivity-73% specificity for grey-scale synovitis score ⩾2, and 80% sensitivity-82% specificity for power Doppler positivity. A stronger agreement was evident between increased knee relative temperature (Δt) and power Doppler positivity (82%) than with clinical examination (76%). In a different patient cohort with painful knees, a knee Δt ⩽0.2 predicted power Doppler positivity with 100% positive and negative predictive values. A thermo-score summing 10 Δt values of three large and seven small RA joints (elbow, knee, ankle, wrist, four hand and two foot joints of the clinically dominant arm or hand and leg or foot) correlated with ultrasound scores of synovitis/tenosynovitis (all P < 0.001) and the 28-joint Disease Activity Score (DAS28) (P = 0.004). The agreement of the thermo-score with ultrasound-defined joint inflammation (82%) was stronger than with DAS28 (64%). The thermo-score improved significantly after 90 days of treatment in patients with active RA at baseline (P = 0.004). Using MRI as reference, Δt of sacroiliac joints could discriminate between spondyloarthritis patients with or without sacroiliitis with 78% sensitivity-74% specificity. CONCLUSION: In-depth increased MWR-derived joint temperature reflects both subclinical and clinically overt inflammation and may serve as a biomarker in arthritis.

Thermoelectric Heat Patch for Clinical and Self-Management: Melanoma Excision Wound Care.

Thermotherapy is considered to have potential beneficial effects when applied to wounds. Of particular relevance to this research are wounds that have dropped in temperature due to regional anaesthesia. This study is aimed at developing a normothermic system comprising of a heat patch controlled by external hardware. The study is divided into three parts: (i) the analyses of the skin temperature that form the foundation of the system; (ii) the development of an efficient wearable heat patch incorporating thermoelectric elements to electrical and thermal conductive textiles; and (iii) the hardware development to control the current flow to the thermoelectric elements thus managing the temperature of the heat patch and conserving current. It was observed that a distance of 3 cm between the thermoelectric elements provides ideal heat distribution relative to the surface area. The system allowed for an 80% reduction in current, while maintaining the temperature of the heat patch at the required thermophysiological skin temperature. Future studies will include development of a temperature sensor identifying the real-time temperature of the wound; and circuitry for switching the polarity of the thermoelectric elements. The cooling capabilities of the thermoelectric elements can be applied to wounds that have increased in temperature.

Microwave Radiometry-Derived Thermal Changes of Small Joints as Additional Potential Biomarker in Rheumatoid Arthritis: A Prospective Pilot Study.

OBJECTIVE: A prospective pilot study was performed using microwave radiometry (MR), a noninvasive method detecting in-depth tissue temperature, to evaluate whether temperature-of-small-joint-derived scores correlate to parameters commonly used to assess disease activity in rheumatoid arthritis (RA). METHODS: Ten patients with active, untreated RA underwent clinical and laboratory assessments and joint ultrasound and MR of hand and foot small joints at baseline and at 15, 30, and 90 days after treatment onset. Mixed-model analysis for repeated measures was used to compare patient characteristics in sequential visits. Twenty age- and sex-matched healthy individuals served as control subjects. RESULTS: Using 1248 MR-derived separate recordings from patients' joints, several thermoscores involving different joint combinations were created. When compared with clinical and ultrasound data, the best performing thermoscore involved temperatures of 16 joints (second to fifth metacarpal and proximal interphalangeal joints, bilaterally). This thermoscore correlated to the 28-joint Disease Activity Score-C-reactive protein, tender and swollen joint counts, patient's visual analog scale (all P ≤ 0.02), and the standard 7-joint ultrasound score (P < 0.03) and could also discriminate patients in high (mean, 9.2 [SD, 5.6]) or moderate (7.1 [SD, 3.5]) versus low disease activity/remission (4.2 [SD, 1.8]) (P ≤ 0.01) or healthy subjects (5.0 [SD, 1.7]) (P = 0.002). CONCLUSIONS: Microwave radiometry-derived increased in-depth temperature indicative of local inflammation of small joints may serve as an additional biomarker in RA. Optimization of MR-based methods may result in objective assessments of RA disease activity in clinical practice.

Multi-center feasibility study of microwave radiometry thermometry for non-invasive differential diagnosis of arterial disease in diabetic patients with suspected critical limb ischemia.

AIMS: Diagnosis of vascular involvement in diabetic foot ulceration (DFU) remains challenging. We conducted a proof of concept study to investigate the feasibility of microwave radiometry (MWR) thermometry for non-invasive differential diagnosis of critical limb ischemia (CLI) in subjects with DFU. METHODS: This prospective, multi-center, study included 80 participants, divided into four groups (group N: normal control subjects; group DN: participants with diabetes and verified neuropathic ulcers without vascular involvement; group DC: participants with diabetes and CLI and group NDC: participants with CLI without diabetes). Vascular disease was confirmed with angiography. All patients underwent MWR (RTM-01-RES:University of Bolton, UK) to record mean tissue temperatures at various pre-determined foot sites. Comparisons of temperature measurements between study groups were performed using one-way ANOVA and Dunn tests. ROC analysis was performed to determine sensitivity, specificity and cut-off value of MWR for CLI diagnosis. RESULTS: Temperatures recorded in vicinity to the foot ulcers of participants with diabetes and CLI were similar to those with CLI without diabetes, but significantly lower than in subjects with neuropathic ulcers without vascular involvement and normal controls (group DC:29.30°C±1.89 vs. group NDC:29.18°C±1.78vs. group N:33.01°C±0.45 vs. group DN:33.39°C±1.37;P<.0001). According to ROC analysis, cut-off temperature value to diagnose CLI was <31.8°C (area under the curve: 0.984; 95% CI: 0.965-1.005;P<.001), with a sensitivity of 100.0% (95%CI: 90.26-100.0) and specificity of 88.37% (95% CI: 74.92-96.11). CONCLUSIONS: Tissue temperatures in vicinity to ulcers were significantly lower in participants with CLI, with or without diabetes, compared to non-ischemic controls. MWR could be used for differential diagnosis of arterial ischemia in subjects with DFU.

Noninvasive detection of increased carotid artery temperature in patients with coronary artery disease predicts major cardiovascular events at one year: Results from a prospective multicenter study.

BACKGROUND AND AIMS: Limited prospective data have been reported regarding the impact of carotid inflammation on cardiovascular events in patients with coronary artery disease (CAD). Microwave radiometry (MWR) is a noninvasive, simple method that has been used for evaluation of carotid artery temperature which, when increased, predicts 'inflamed' plaques with vulnerable characteristics. We prospectively tested the hypothesis that increased carotid artery temperature predicts future cerebro- and cardiovascular events in patients with CAD. METHODS: Consecutive patients from 3 centers, with documented CAD by coronary angiography, were studied. In both carotid arteries, common carotid intima-media thickness and plaque thickness were evaluated by ultrasound. Temperature difference (ΔT), measured by MWR, was considered as the maximal temperature along the carotid artery minus the minimum; ΔT ≥0.90 °C was assigned as high. Major cardiovascular events (MACE, death, stroke, myocardial infarction or revascularization) were recorded during the following year. RESULTS: In total, 250 patients were studied; of them 40 patients (16%) had high ΔT values in both carotid arteries. MACEs occurred in 30% of patients having bilateral high ΔT versus 3.8% in the remaining patients (p<0.001). Bilateral high ΔT was independently associated with increased one-year MACE rate (HR = 6.32, 95% CI 2.42-16.53, p<0.001, by multivariate cox regression hazard model). The addition of ΔT information on a baseline model based on cardiovascular risk factors and extent of CAD significantly increased the prognostic value of the model (c-statistic increase 0.744 to 0.845, pdif = 0.05) CONCLUSIONS: Carotid inflammation, detected by MWR, has an incremental prognostic value in patients with documented CAD.

Inflamed human carotid plaques evaluated by PET/CT exhibit increased temperature: insights from an in vivo study.

AIMS: To explore the relationship between temperature measurements derived by microwave radiometry (MWR) and carotid flurodeoxyglucose (FDG) uptake and assess their association with histological and immunohistochemistry findings in patients with high-grade carotid stenosis. METHODS AND RESULTS: In 21 patients undergoing carotid endarterectomy, carotid inflammation was evaluated by both FDG positron emission/computed tomography (FDG-PET/CT) imaging and MWR measurements. Carotid inflammation was assessed by PET/CT as target-to-background ratio (TBR) by obtaining measurements in consecutive axial slices 2 cm below to 2 cm above the carotid bifurcation. Temperature difference (ΔT) by MWR was assigned as the maximum-minimum temperature measurements over the corresponding carotid segments. The extent of lipid core, calcification as well as CD68 and CD31 levels were also assessed. There was a significant correlation between ΔT values and FDG uptake (R = 0.40, P = 0.01), but no correlation between the degree of angiographic stenosis and ΔT values (R = -0.02, P = 0.91) or PET/CT measurements (R = -0.28, P = 0.86). Patients with plaques containing high lipid core extension or low calcification exhibited higher ΔT (P = 0.001 and P < 0.001, respectively) and FDG uptake values (P = 0.02 and P = 0.02, respectively). Patients with plaques containing increased CD68 expression exhibited higher ΔT and FDG uptake measurements. CONCLUSION: Carotid plaque inflammation was evaluated by temperature measurements, which were correlated with FDG-PET/CT indices, confirmed by histopathology and immunohistochemistry findings. Structural changes did not predict inflammatory process. The implications of these findings in risk stratification and management of patients with carotid atherosclerosis and the precise algorithm for potential clinical utilization of MWR and PET/CT remain to be determined.

Female gender is independently associated with increased carotid temperatures in patients with coronary artery disease.

BACKGROUND: Limited are the data regarding the sex differences in functional carotid artery characteristics. Microwave Radiometry (MWR) is a new noninvasive method, which measures in vivo instantly the internal temperatures of tissues, reflecting inflammation. The aim of the present study was to investigate whether in patients with coronary artery disease (CAD), gender related differences apply in carotid plaque functional characteristics, as assessed by MWR. METHODS: Consecutive patients with significant CAD were included in the study. All patients underwent evaluation of both carotid arteries by 1) ultrasound and 2) MWR. During ultrasound common carotid IMT and plaque thickness were assessed according to Mannheim consensus. During MWR measurements, temperature difference (ΔT) was assigned as maximal temperature along the carotid artery minus minimum. ΔT ≥0.90°C was assigned as high ΔT. RESULTS: In total 364 patients with significant CAD were included in the study. Of these 54 were female and 310 were male. Max plaque thickness and ccIMT were similar between males and females (2.38±1.16 vs. 2.46±1.12mm, p=0.63 and 0.944±0.172 vs. 0.942±0.169mm, p=0.96). Carotid arteries of females showed higher ΔT values (1.16±0.48 vs 0.87±0.45°C, p<0.001). Interestingly, females had more commonly high ΔT values bilaterally (35.2% vs 15.5%, p=0.001). In multivariate analysis, female sex was independently associated with bilateral high ΔT, when adjusted to potential covariates (OR=2.78, 95% CI=1.42-5.45, p=0.003). CONCLUSIONS: In patients with CAD, sex specific differences apply in functional but not in structural carotid artery characteristics. Whether this discrepancy has prognostic significance, remains to be clarified in future studies.

Bilateral symmetry of local inflammatory activation in human carotid atherosclerotic plaques.

INTRODUCTION: Only a few studies have investigated the structural and functional characteristics of carotid arteries bilaterally. Furthermore, there is controversy as to whether inflammation in paired vascular beds is a local or systemic phenomenon. We aimed to examine, in patients with coronary artery disease, whether intra-subject left and right carotid arteries have similar inflammatory status, as determined non-invasively by microwave radiometry (MWR). METHODS: Consecutive patients (n=200) with significant coronary artery disease were evaluated via an ultrasound echo-colour Doppler (US-ECD) study of both carotid arteries and temperature measurements with MWR. During thermography, thermal heterogeneity (ΔT) was defined as the maximum temperature along the carotid artery minus the minimum temperature. RESULTS: Mean T was similar between the left and right carotid arteries (0.78 ± 0.48 vs. 0.84 ± 0.52°C, p=0.12). Mean right intima-media thickness (IMT) was greater compared to mean left IMT (2.16 ± 1.20 vs. 1.93 ± 0.94 mm, p<0.01). In all carotids, there was a correlation between left and right carotid plaque ΔT (R=0.38, p<0.001) and between left and right IMT (R=0.48, p<0.001). Independent predictors for the presence of bilateral carotid plaques were found to be the extent of coronary artery disease, high ΔT, and therapy with angiotensin II receptor blockers; predictors for the presence of high ΔT bilaterally were bilateral carotid plaques, male sex, diabetes mellitus, and hypertension. CONCLUSIONS: There is bilateral inflammatory activation in the carotid atherosclerotic lesions of patients with coronary artery disease. At this stage of carotid disease, arterial hypertension and diabetes mellitus are more strongly correlated with bilateral functional abnormalities in carotid plaques than with structural changes.

Incremental predictive value of carotid inflammation in acute ischemic stroke.

BACKGROUND AND PURPOSE: Microwave Radiometry (MWR) allows in vivo noninvasive assessment of internal temperature of tissues. The aim of the present study was to evaluate in patients with ischemic stroke and bilateral carotid plaques (1) whether ipsilateral carotid arteries exhibit higher temperature differences (ΔT), as assessed by MWR; (2) the predictive accuracy of MWR in symptomatic carotid artery identification. METHODS: Consecutive patients with recent acute anterior circulation ischemic stroke because of large artery atherosclerosis were included in the study. Carotid arteries of all patients were evaluated by carotid ultrasound and MWR. RESULTS: In total, 50 patients were included in the study. Culprit carotid arteries had higher ΔT compared with nonculprit (0.93±0.58 versus 0.58±0.35°C; P<0.001). The addition of ΔT to a risk prediction model based only on ultrasound plaque characteristics increased its predictive accuracy significantly (c-statistic: 0.691 versus 0.768; Pdif=0.05). CONCLUSIONS: Culprit carotid arteries show higher thermal heterogeneity compared with nonculprit carotid arteries in patients with acute ischemic stroke and bilateral carotid plaques. MWR has incremental value in culprit carotid artery discrimination.

Preparation and characterisation of thermoresponsive nanogels for smart antibacterial fabrics.

The present investigation involves the preparation and characterisation of silver containing nanogels and their incorporation onto the surface of woven fabrics so that they can be potentially used in biomedical applications such as wound dressings. These silver nanoparticles were mixed with N-isopropylacrylamide (NIPAM) based nanogels during and at the end of polymerisation process prior to their application onto the fabrics. NIPAM based nanogels were found to have a peak of lower critical solution temperature (LCST) that is close to the human body temperature. These nanogels were applied on cotton fabrics and cured for 15 h at 30°C. Silver based nanogels were padded onto the fabrics followed by drying at 30°C overnight. Scanning electron microscopy images have shown excellent distribution of silver nanoparticles on the fabric surface. EDX analysis was also conducted to confirm the presence of silver particles on the fabric surface. The results showed that a cotton fabric treated with silver based nanogels prevented the growth of bacteria, i.e. Gram-positive (Staphylococcus epidermidis) and Gram-negative (Escherichia coli), on whereas the control cotton fabric samples exhibited considerable level of bacterial growth. Specifically, the nanogels in which the silver particles were added during the polymerisation process were observed to have higher antibacterial efficacy towards both types of bacteria.

Morphological and functional assessment of carotid plaques have similar predictive accuracy for coronary artery disease.

BACKGROUND AND PURPOSE: Microwave radiometry allows noninvasive in vivo measuring of internal temperature of tissues reflecting inflammation. In the present study, we evaluated the predictive accuracy of this method for the diagnosis of coronary artery disease (CAD). METHODS: Consecutive patients (n=287) scheduled for coronary angiography were included in the study. In carotid arteries of both groups, the following measurements were performed: (1) intima-media thickness (IMTmax) and (2) temperature measurements by microwave radiometry (ΔTmax). C-statistic and net reclassification improvement were used to compare the prediction ability of the markers IMTmax and ΔTmax for the presence of CAD and multivessel CAD. RESULTS: Of 287 patients, 239 had stenoses ≥50% (CAD group), and 48 did not have significant stenoses (NO-CAD group). ΔTmax was an independent predictor for the presence of CAD and multivessel CAD, showing similar predictive accuracy to intima-media thickness, as assessed by c-statistic and net reclassification improvement. CONCLUSIONS: Local inflammatory activation, as detected by microwave radiometry, has similar predictive accuracy to intima-media thickness for the presence and extent of CAD.

Detection of subclinical synovial inflammation by microwave radiometry.

OBJECTIVE: Microwave Radiometry is a non-invasive method which determines within seconds the in vivo temperature of internal tissues at a depth of 3-7 cm with an accuracy of ±0.2°C. In this proof-of-concept study, we tested the hypothesis that, in absence of relevant clinical signs, increased local temperature detected by microwave radiometry reflects subclinical synovial inflammation, using ultrasound as reference method. METHODS: Knees of healthy controls, subjects with recent knee trauma and symptom-free patients with rheumatoid arthritis (RA) or osteoarthritis were examined by placing the microwave radiometry sensor, a) at the upper one third of the anterior surface of the thigh (control-point), and b) over the suprapatellar recess. Ultrasound was performed immediately after and the possible presence of fluid and/or synovitis was correlated with microwave radiometry findings. RESULTS: In 30 healthy and 10 injured knees the temperature was always lower than thigh (32.3±1.1 and 31.8±1.4 versus 34.1±0.9 and 33.6±1.2°C with a difference (ΔΤ) of -1.8±0.2 and -1.9±0.4°C respectively). Of 40 RA and 20 osteoarthritis knees examined, ultrasound findings indicative of subclinical inflammation (fluid effusion and/or Doppler signal) were found in 24 and 12, respectively, in which the temperature was higher than healthy knees and ΔΤ was lower (-0.9±0.7 in RA and -1.0±0.5 in osteoarthritis versus -1.8±0.2°C, p<0.001). The 5 RA knees with power Doppler findings indicative of grade 2 inflammation had a ΔΤ 3 times lower compared to healthy (-0.6±0.6, p = 0.007), whereas the 9 RA and the 7 osteoarthritis knees with additionally fluid effusion, had even lower ΔΤ (-0.4±0.7, p<0.001). CONCLUSION: Using a safe, rapid and easy-to-perform method, such as microwave radiometry, thermal changes within the knee joint may reflect non-clinically apparent joint inflammation. Refinement of this method, including production of sensors for small joints, could result to the development of the ideal objective tool to detect subclinical synovitis in clinical practice.

Sedimentation behaviour in electrorheological fluids based on suspensions of zeolite particles in silicone oil.

Sedimentation is a known and expected shortcoming of electrorheological fluids (ERFs) due to the inherent difference in the constituent densities. The long-term sedimentation causes loss of the electrorheological phenomenon and the exploitable electromechanical and viscoelastic properties despite the presence of the stimulating electric field. In this work, we report the effect of temperature and surfactant concentration on the stability of ERFs prepared from zeolite particles and silicone oil with primary focus on the sedimentation of the particles in the ERF. As the temperature stability of the ERFs is fundamentally important, we have studied three different ERF suspensions composed of different zeolite particles, in silicone oil. These ERFs have been comparatively evaluated for their sedimentation over time, across a wide range of temperatures (-40°C to +60°C). The influence of surfactant concentration on the colloidal stability of the ERFs has also been investigated. A novel method of acoustic stirring (kHz range) on the homogenisation of the ERFs has been proposed and its effect on the sedimentation process evaluated. These results are useful for assessment of alternative suspension methods for specific applications.

In vivo measurement of plaque neovascularisation and thermal heterogeneity in intermediate lesions of human carotid arteries.

OBJECTIVES: Both neoangiogenesis and inflammation contribute in atherosclerosis progression. Contrast-enhanced ultrasound (CEUS) provides visualisation of plaque neovascularisation. Microwave radiometry (MR) allows in vivo non-invasive measurement of temperature of tissues, reflecting inflammatory activation. We assessed the association of carotid plaque temperature, measured by MR, with plaque neovascularisation assessed by CEUS in intermediate lesions. METHODS: Consecutive patients with coronary artery disease and carotid atherosclerosis underwent carotid ultrasound imaging, CEUS and MR. Plaque texture, plaque surface and plaque echogenicity were analysed. Contrast enhancement (CE) by CEUS was defined as the % percentage of signal intensity difference, prior and post contrast infusion. Thermal heterogeneity (ΔT) was assigned as maximal temperature along the carotid artery minus minimum. RESULTS: Eighty-six carotid arteries of 48 patients were included. Fatty plaques had higher CE% and ΔT compared with mixed and calcified (p<0.01 for all comparisons). Heterogeneous plaques had higher CE% and ΔT compared with homogenous (p<0.01 for all comparisons). Plaques with irregular surface had higher CE% and ΔT compared with plaques with regular (p<0.01 for all comparisons). There was a good correlation between ΔT and CE (R=0.60, p<0.001). CONCLUSIONS: Carotid plaque neovascularisation on CEUS examination is associated with increased thermal heterogeneity and ultrasound characteristics of plaque vulnerability in intermediate lesions.

First in vivo application of microwave radiometry in human carotids: a new noninvasive method for detection of local inflammatory activation.

OBJECTIVES: This study investigated whether temperature differences: 1) can be measured in vivo noninvasively by microwave radiometry (MR); and 2) are associated with ultrasound and histological findings. BACKGROUND: Studies of human carotid artery samples showed increased heat production. MR allows in vivo noninvasive measurement of internal temperature of tissues. METHODS: Thirty-four patients undergoing carotid endarterectomy underwent screening of carotid atherosclerosis by ultrasound and MR. Healthy volunteers were enrolled as a control group. During ultrasound study, plaque texture, plaque surface, and plaque echogenicity were analyzed. Temperature difference (ΔT) was assigned as maximal minus minimum temperature. Association of thermographic with ultrasound and histological findings was performed. RESULTS: ΔT was higher in atherosclerotic carotid arteries compared with the carotid arteries of controls (p < 0.01). Fatty plaques had higher ΔT compared with mixed and calcified (p < 0.01) plaques. Plaques with ulcerated surface had higher ΔT compared with plaques with irregular and regular surface (p < 0.01). Heterogeneous plaques had higher ΔT compared with homogenous (p < 0.01). Specimens with thin fibrous cap and intense expression of CD3, CD68, and vascular endothelial growth factor (VEGF) had higher ΔT compared with specimens with thick cap and low expression of CD3, CD68, and VEGF (p < 0.01). CONCLUSIONS: MR provides in vivo noninvasive temperature measurements of carotid plaques, reflecting plaque inflammatory activation.

Generation of microwave-induced plasmas in automotive exhaust gas mixtures using pulsed microwave energy.

Microwave energy at 2.45 GHz was applied to a mixture of exhaust gases from a petrol engine at atmospheric pressure. It was found that by pulsing the microwave energy with a 50% duty cycle, the average power required to sustain a microwave-induced plasma discharge was decreased by about 40%. The ratio of absorbed to incident power was unaffected. These findings were confirmed for pulse frequencies from 10 to 300 Hz.