Costanzo Di Maria

Novel assessment of microvascular changes in idiopathic restless legs syndrome (Willis–Ekbom disease)

Many patients with restless legs syndrome (Willis–Ekbom disease) complain of burning sensations in their feet associated with the desire to move, such that they seek cooler environments. This pilot study aimed to characterise the microvascular skin changes in 12 patients with restless legs syndrome compared with 12 age‐ and sex‐matched controls. Patients with moderate or severe restless legs syndrome and controls underwent detailed thermovascular assessment in a controlled temperature room at three different stages (normothermic phase 23 °C, hot phase 30 °C, cold phase 18 °C). Microvascular activity was recorded during all phases by bilateral great toe laser‐Doppler flowmetry and also by whole‐body thermography. Patient and control measurements were compared. The study protocol was well tolerated. Parameters extracted from the laser‐Doppler flowmetry measurements were used to model a logistic function using binary logistic regression. This demonstrated a statistically significant difference between patients with restless legs syndrome and healthy controls (P < 0.001). Visual inspection of the body thermography image sequences showed increased lower limb movement in patients with restless legs syndrome patients compared with controls. Thermography analysis also showed significant differences between foot temperatures in patients with restless legs syndrome compared with controls during the hot phase (P = 0.011). Notably, patients with restless legs syndrome had more uniform foot temperatures, whereas controls had a wider variability in surface temperature across the feet. This novel study demonstrates impaired microvascular circulation in patients with restless legs syndrome in comparison to matched controls and a potential mechanism for the sensation of burning feet. The protocol also provides an experimental paradigm to test therapeutic interventions for the future.

Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis–a new potential diagnostic biomarker

Autonomic nervous system dysfunction is frequently reported in chronic fatigue syndrome (CFS) with orthostatic intolerance, a common symptom that can be objectively assessed. The frequent finding of autonomic dysfunction and symptoms on standing has the potential to provide a diagnostic biomarker in chronic fatigue. In this study we explored the clinical value of non-invasive optical multi-site photoplethysmography (PPG) technology to assess cardiovascular responses to standing. Multi-site PPG pulses were collected from tissue pads of the ears, fingers and toes of 14 patients with CFS and 14 age-matched sedentary subjects using a measurement protocol of a 10 min baseline (subject supine) followed by 3 min of tilting on a tilt table (head-up to 70°). Percentage change in pulse timing (pulse transit time, PTTf) and pulse amplitude (AMP) at each site were calculated using beat-to-beat pulse wave analysis. A significant reduction in the overall pulse timing response to controlled standing was found for the CFS group (using summed absolute percentage change in PTTf for ear, finger and toe sites, median change of 26% for CFS and 37% for control with p = 0.002). There were no significant differences between subject groups for the AMP measure at any site. Changes in AMP with tilt were, however, weakly significantly and negatively correlated with fatigue severity (p < 0.05). Receiver operating characteristic (ROC) analysis of timing measures produced an area under the curve of 0.81. Experimental linear discriminant classification analysis comparing both timing and amplitude measures produced an overall diagnostic accuracy of 82%. Pulse wave abnormalities have been observed in CFS and represent a potential objective measure to help differentiate between CFS patients and healthy controls.

Extracting fetal heart beats from maternal abdominal recordings: selection of the optimal principal components.

This study presents a systematic comparison of different approaches to the automated selection of the principal components (PC) which optimise the detection of maternal and fetal heart beats from non-invasive maternal abdominal recordings.A public database of 75 4-channel non-invasive maternal abdominal recordings was used for training the algorithm. Four methods were developed and assessed to determine the optimal PC: (1) power spectral distribution, (2) root mean square, (3) sample entropy, and (4) QRS template. The sensitivity of the performance of the algorithm to large-amplitude noise removal (by wavelet de-noising) and maternal beat cancellation methods were also assessed. The accuracy of maternal and fetal beat detection was assessed against reference annotations and quantified using the detection accuracy score F1 [2*PPV*Se / (PPV + Se)], sensitivity (Se), and positive predictive value (PPV). The best performing implementation was assessed on a test dataset of 100 recordings and the agreement between the computed and the reference fetal heart rate (fHR) and fetal RR (fRR) time series quantified.The best performance for detecting maternal beats (F1 99.3%, Se 99.0%, PPV 99.7%) was obtained when using the QRS template method to select the optimal maternal PC and applying wavelet de-noising. The best performance for detecting fetal beats (F1 89.8%, Se 89.3%, PPV 90.5%) was obtained when the optimal fetal PC was selected using the sample entropy method and utilising a fixed-length time window for the cancellation of the maternal beats. The performance on the test dataset was 142.7 beats(2)/min(2) for fHR and 19.9 ms for fRR, ranking respectively 14 and 17 (out of 29) when compared to the other algorithms presented at the Physionet Challenge 2013.

Novel photoplethysmography cardiovascular assessments in patients with Raynaud’s phenomenon and systemic sclerosis: a pilot study

OBJECTIVE Multisite photoplethysmography (PPG) cardiovascular assessments can evaluate endothelial, peripheral autonomic and arterial dysfunction. The aim of this pilot study was to investigate the potential clinical utility of the technology in assessing patients with SSc and primary RP (PRP). METHODS Multisite PPG pulse measurements, a reference ankle brachial pressure index (ABPI) and a full clinical assessment were undertaken for three subject groups: SSc, PRP and controls. Endothelial and autonomic function and arterial disease measures were obtained using pulse wave analysis. RESULTS Nineteen SSc, 19 PRP and 23 control subjects were assessed and compared. Endothelial function was significantly impaired in SSc (P < 0.02), but with no difference between controls and PRP. Receiver operating characteristic-based classification accuracy was 81% (sensitivity 90%, specificity 74%) for separating SSc from controls and 82% (sensitivity 84%, specificity 79%) for separating SSc from PRP. SSc patients with digital ulcers had significantly lower endothelial function compared with those without ulcers (P < 0.05). Autonomic dysfunction was suggested in both SSc and PRP and was most exaggerated in patients with diffuse SSc. All groups had overall normal ABPI and arterial stiffness timing measures. Bilateral timing differences at the toes, which represents peripheral occlusive arterial disease, did show increased asymmetry in SSc (P < 0.02). CONCLUSION Multisite PPG pulse technology showed potential diagnostic ability. By using measures of endothelial function, it differentiated SSc from control and PRP subjects with an accuracy of at least 81%. Objective pulse-derived measures of autonomic function and arterial disease in SSc have also been reported in this pilot study.

Quantifying the correlation between photoplethysmography and laser Doppler flowmetry microvascular low-frequency oscillations

Abstract. Photoplethysmography (PPG) and laser Doppler flowmetry (LDF) are two recognized optical techniques that can track low-frequency perfusion changes in microcirculation. The aim of this study was to determine, in healthy subjects, the correlation between the techniques for specific low-frequency bands previously defined for microcirculation. Twelve healthy male subjects (age range 18 to 50 years) were studied, with PPG and LDF signals recorded for 20 min from their right and left index (PPG) and middle (LDF) fingers. Wavelet analysis comprised dividing the low-frequency integral wavelet spectrum (IWS) into five established physiological bands relating to cardiac, respiratory, myogenic, neurogenic, and endothelial activities. The correlation between PPG and LDF was quantified using wavelet correlation analysis and Spearman correlation analysis of the median IWS amplitude. The median wavelet correlation between signals (right-left side average) was 0.45 (cardiac), 0.49 (respiratory), 0.86 (myogenic), 0.91 (neurogenic), and 0.91 (endothelial). The correlation of IWS amplitude values (right-left side average) was statistically significant for the cardiac (ρ=0.64, p<0.05) and endothelial (ρ=0.62, p<0.05) bands. This pilot study has shown good correlation between PPG and LDF for specific physiological frequency bands. In particular, the results suggest that PPG has the potential to be a low-cost replacement for LDF for endothelial activity assessments.

Innovative multi-site photoplethysmography measurement and analysis demonstrating increased arterial stiffness in paediatric heart transplant recipients

OBJECTIVE It has been documented that heart transplantation in children is often complicated by arterial hypertension and increased arterial stiffness. We use innovative multi-site photoplethysmography (MPPG) pulse measurement and analysis technology to assess changes in arterial stiffness in paediatric heart transplant recipients (HTRs) in comparison with healthy control (HC) children. APPROACH A group of 20 HTRs (median age 13.5 years, eight male) were compared to an overall age- and gender-matched group of 161 HCs (median age 11.6 years, 74 male). Peripheral pulse was recorded bilaterally using MPPG at the ear lobe, index finger and great toe sites, along with an electrocardiogram cardiac timing reference. Segmental pulse arrival times between peripheral sites (finger-ear, PATf-e; toe-finger, PATt-f; and toe-ear PATt-e) were calculated as arterial stiffness measures, and differences between subject groups were tested using multivariate analysis. Normalised ear, finger and toe pulse shapes were also studied and compared between groups. MAIN RESULTS After correction for heart rate and diastolic and mean arterial blood pressures, the HTR group was found to have significantly lower segmental PATt-e and PATt-f measurements, with median values of 150 ms versus 172 ms in the HC group (p  =  0.02), and 104 ms versus 118 ms in the HC group (p  =  0.01), respectively, consistent with increased arterial stiffness in the patient group. The normalised ear, finger and toe sites showed only a mild elongation in each pulse rise time for the transplant group. SIGNIFICANCE This study shows that innovative and easy-to-do MPPG gives further evidence for increased arterial stiffness in children who have undergone successful cardiac transplantation.

Novel optical assessments of tissue composition and viability using fluorescence spectroscopy and tissue oxygenation spectrophotometry in patients with systemic sclerosis - a pilot study

OBJECTIVE Patients with systemic sclerosis (SSc) experience significant morbidity and mortality, therefore, the development of tests to aid its early diagnosis are very important. The aim of this pilot study was to assess the diagnostic value of novel optical non-invasive skin fluorescence spectroscopy (FS) and tissue oxygen saturation (TOS) viability measurements in patients with established SSc. APPROACH Two groups were studied, comprising 14 SSc patients and nine healthy controls (93% and 73% females, respectively). FS and TOS measurements were collected from three body sites: the forearm, chest, and calf. Fluorescence intensities at wavelengths attributed to collagen, elastin, and L-tryptophan were computed, with adjustment for melanin, and a normalised combined fluorescence score (NCFS) was determined. MAIN RESULTS The NCFS was significantly higher (p  <  0.001) and the combined TOS significantly lower (p  <  0.001) in the SSc group. TOS measurements alone showed good classification accuracy (95.7%) at separating SSc from healthy control participants, with some clustering of values close to the 50% oxygenation level in both groups. When the composition and viability measures were combined and modelled using binary logistic regression, excellent results for the sample were obtained following leave one out cross validation (100%). SIGNIFICANCE The results of this pilot study demonstrate the potential diagnostic utility of FS and TOS assessments in SSc patients and further work is now needed to validate these techniques prospectively in a larger group of SSc patients across the spectrum of the disease, and also patients with other types of vasculopathy and conditions that can cause skin fibrosis.

Intraoperative Thermal and Laser Speckle Contrast Imaging Assessment of Bowel Perfusion in Two Cases of Colorectal Resection Surgery

The Microvascular Diagnostics Service at Freeman Hospital, Newcastle upon Tyne, holds a comprehensive range of optical and thermal technologies utilised to study the microcirculation both for clinical and research purposes. In the recent years, collaboration has been formed with the colorectal surgical service to look at the feasibility and clinical value of intraoperatively assessing bowel perfusion using microvascular imaging technologies. Anastomotic failure is the most serious complication following colorectal resection that can lead to re-operation, permanent stoma, and even death. The current practice of assessing blood perfusion at the anastomosis bowel ends by direct inspection of bowel pulsatility, bleeding, and tissue coloration has been demonstrated to lack predictive accuracy. The medical community is striving to improve the outcome of colorectal resections and a key aspect in achieving this goal will be the development of more objective techniques to intraoperatively assess and quantify the bowel perfusion. We believe that microvascular imaging technology could play a key role in this respect. In this chapter, we describe two case studies which show the feasibility of performing thermal and laser speckle contrast imaging measurements intraoperatively for assessing bowel perfusion during colorectal resection surgery. This experience could pave the way to a number of other applications for these technologies in the surgical arena.