COMPUTER-AIDED QUANTITATIVE EARLY DIAGNOSIS OF DIABETIC FOOT

Diabetes is an incurable metabolic disease characterized by high blood sugar levels. The feet of people with diabetes are at the risk of a variety of pathological consequences including peripheral vascular disease, deformity, ulceration, and ultimately amputation. The key to managing the diabetic foot is prevention and early detection. Unfortunately, current hospital centered reactive diabetes care and the availability of inadequate qualitative diagnostic screening procedures causes physicians to miss the diagnosis in 61% of the patients. We have developed a computer aided diagnostic system for early detection of diabetic foot. The key idea is that diabetic foot exhibits significant neuropathic and vascular damages. When a diabetic foot is placed under cold stress, the thermal recovery will be much slower. This thermal recovery speed can be a quantitative measure for the diagnosis of diabetic foot condition. In our research, thermal recovery of the feet following cold stress is captured using an infrared camera. The captured infrared video is then filtered, segmented, and registered. The temperature recovery at each point on the foot is extracted and analyzed using a thermal regulation model, and the problematic regions are identified. In this thesis, we present our research on the following aspects of the developed computer aided diagnostic systems: subject measurement protocols, a trustful numerical model of the camera noise and noise parameter estimations, infrared video segmentation, new models of thermal regulations, thermal patterns classifications, and our preliminary findings based on small scale clinical study of about 40 subjects, which demonstrated the potential the new diagnostic system

Contactless photoplethysmography for assessment of small fiber neuropathy

Chronic pain is a prevalent condition affecting approximately one-fifth of the global population, with significant impacts on quality of life and work productivity. Small fiber neuropathies are a common cause of chronic pain, and current diagnostic methods rely on subjective self-assessment or invasive skin biopsies, highlighting the need for objective noninvasive assessment methods. The study aims to develop a modular prototype of a contactless photoplethysmography system with three spectral bands (420, 540, and 800 nm) and evaluate its potential for assessing peripheral neuropathy patients via a skin topical heating test and spectral analyses of cutaneous flowmotions. The foot topical skin heating test was conducted on thirty volunteers, including fifteen healthy subjects and fifteen neuropathic patients. Four cutaneous nerve fiber characterizing parameters were evaluated at different wavelengths, including vasomotor response trend, flare area, flare intensity index, and the spectral power of cutaneous flowmotions. The results show that neuropathic patients had significantly lower vasomotor response (50%), flare area (63%), flare intensity index (19%), and neurogenic component (54%) of cutaneous flowmotions compared to the control group, independent of photoplethysmography spectral band. An absolute value of perfusion was 20%–30% higher in the 420 nm band. Imaging photoplethysmography shows potential as a cost-effective alternative for objective and non-invasive assessment of neuropathic patients, but further research is needed to enhance photoplethysmography signal quality and establish diagnostic criteria

IRlab - Platform for thermal video analysis in evaluation of peripheral thermal behavior and blood perfusion

Background and objectives: Dynamic thermal imaging in medicine has several advantages in comparison to static thermal image analysis and has potential as a novel patient assessment method e.g. in the area of vascular surgery. Since dynamic thermal imaging has become in the scope of research only during the last decade, the computational available analysis methods are often lacking or not existing. Most of the published software is not available to the research community or are behind a paywall. IRlab provides an easy-to-use dynamic thermal video processing and analysis platform, freely accessible to researchers. Methods: IRlab is programmed in Matlab R2020b. Computational tools for dynamic analysis are divided into spatio-temporal and spectral methods, where spatio-temporal methods consist of region of interest delineation tools, thermal modulation analysis, standard thermal measures such as median, maximum, minimum and deviation values, and subtraction and gamma maps. Spectral methods include spectral band power, spectral flow, and wavelet analysis tools. Preliminary data of a single healthy subject was analyzed with the program as a sample run. Results: IRlab provides a platform for lower limb thermal image and video analysis with a clear workflow and variety of processing and analysis tools for time and frequency space analysis. The whole source code for IRlab is freely available for the research community under the General public license. Conclusions: IRlab is a versatile tool for dynamic thermal image and video processing. Freeware and open-source programs for medical thermal imaging are severely lacking, thus as a completely open-source project IRlab offers a unique platform for researchers within the field of medical thermal imaging.publishedVersionPeer reviewe

Assessment of chronic limb threatening ischemia using thermal imaging

Objectives: Current chronic limb threatening ischemia (CLTI) diagnostics require expensive equipment, using ionizing radiation or contrast agents, or summative surrogate methods lacking in spatial information. Our aim is to develop and improve contactless, non-ionizing and cost-effective diagnostic methods for CLTI assessment with high spatial accuracy by utilizing dynamic thermal imaging and the angiosome concept. Approach: Dynamic thermal imaging test protocol was suggested and implemented with a number of computational parameters. Pilot data was measured from 3 healthy young subjects, 4 peripheral artery disease (PAD) patients and 4 CLTI patients. The protocol consists of clinical reference measurements, including ankle- and toe-brachial indices (ABI, TBI), and a modified patient bed for hydrostatic and thermal modulation tests. The data was analyzed using bivariate correlation. Results: The thermal recovery time constant was on average higher for the PAD (88%) and CLTI (83%) groups with respect to the healthy young subjects. The contralateral symmetry was high for the healthy young group and low for the CLTI group. The recovery time constants showed high negative correlation to TBI (ρ = -0.73) and ABI (ρ = -0.60). The relation of these clinical parameters to the hydrostatic response and absolute temperatures (|ρ|<0.3) remained unclear. Conclusion: The lack of correlation for absolute temperatures or their contralateral differences with the clinical status, ABI and TBI disputes their use in CLTI diagnostics. Thermal modulation tests tend to augment the signs of thermoregulation deficiencies and accordingly high correlations were found with all reference metrics. The method is promising for establishing the connection between impaired perfusion and thermography. The hydrostatic modulation test requires more research with stricter test conditions.publishedVersionPeer reviewe

THETA BURST BRAIN STIMULATION IN PAINFUL DIABETIC NEUROPATHY PATIENTS: INVESTIGATING NEURAL MECHANISMS

Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management for pDN due to the paucity of disease-modifying therapies targeting the irreversible nerve damage from DN. Noninvasive brain stimulation using transcranial magnetic stimulation (TMS) has been utilized as a therapeutic tool in patients with neuropsychiatric disorders, and has only been used in CP patients for research purposes. Previous studies have consistently reported the analgesic effects of high frequency repetitive TMS (HF-rTMS) via stimulation of the primary motor cortex (M1) in patients with NP. Another cortical target that has been studied using rTMS is the Dorsolateral Prefrontal Cortex (DLPFC). More recently, rTMS paradigms such as theta burst stimulation (TBS) have been developed that require less stimulation time (1-4 minutes) and lower stimulation intensities than conventional HF-rTMS protocols. TBS can be provided using either the intermittent or continuous paradigms. A prolonged form of continuous TBS (pcTBS) produces facilitatory and analgesic effects similar to HF-rTMS. No study has examined the analgesic effects of pcTBS targeted at the M1 and DLPFC brain regions in pDN patients, and concomitantly evaluated neural mechanisms of pain perception. Therefore, the central aim of this dissertation is to examine the effectiveness of pcTBS as an intervention in pDN patients by targeting the M1 and DLPFC regions of the brain, and to investigate the neural mechanisms that may explain the changes in pain perception. Therefore, Study 1 (Chapter 3) examined the efficacy of pcTBS targeted at the M1 and DLPFC brain regions as an intervention in pDN patients with a single session, prospective, single-blind, sham-controlled, randomized clinical trial. Study 2 (Chapter 4) investigated the neural mechanisms that could potentially explain the effects of pcTBS targeted at the M1 and DLPFC brain regions on pain perception in patients with pDN; (a) psychophysical mechanisms that comprise of the descending and ascending endogenous pain modulatory systems (b) neurophysiological mechanisms of corticospinal excitability, and (c) intracortical inhibition measures linked to GABA activity. The main findings from this dissertation are that pcTBS targeted at M1 or DLPFC may constitute an effective analgesic treatment for pDN and neurophysiological mechanisms related to corticospinal excitability and neurochemical mechanisms linked to intracortical inhibition may explain the analgesic response to pcTBS stimulation at the M1 and DLPFC brain regions in patients with pDN. Chapter 2 presents a review of the literature on brain derived neurotrophic factor (BDNF), focusing on its role as a biomarker, its mechanism of action in NP, and a critical analysis of the quantification of BDNF in serum and plasma

Clinical utility of near-infrared spectroscopy in skeletal muscle : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy (Sport and Exercise Science) at Massey University, Wellington, New Zealand

The following Figures were removed for copyright reasons: Figure 3.3 (=Ferrari et el., 2004 Fig 1B) and Figure 3.7 (=Yamashita et al., 2013 Fig 1.14 page 15). Figures 3.5 and 3.10 are reproduced under a Creative Commons Attribution 4.0 International (CC BY 4.0) license. Possibly copyrighted Figures from Van Beekvelt et al. (2001) remain for clarity's sake.Introduction: Near infrared spectroscopy (NIRS) provides for non-invasive assessment of resting skeletal muscle hemodynamic and respiratory responses. However, the interday reliability of skeletal muscle blood flow (mBF) and oxygen consumption (mV̇O2) responses to stressors such as exercise in both healthy and clinical populations has not been established. Moreover, direct comparison of differing NIRS technologies is absent. The purpose of this thesis is three-fold 1) establish a standard protocol for the assessment of resting and exercise skeletal muscle hemodynamics for healthy and clinical populations, 2) compare the reliability of NIRS outcomes in continuous wave (cw) NIRS to the more robust frequency domain (fd) NIRS technology, and 3) assess validity against in-vitro skeletal muscle metabolic parameters. Methods: In the first study, a standard protocol developed to measure mBF, mV̇O2, and perfusion ([tHb]) in the vastus lateralis (VL) at rest and up to 30% of maximum voluntary contraction and mV̇O2 recovery rate constant (k) as an index of muscle oxidative capacity was conducted in twelve healthy adults and was repeated twice within 10 days to establish repeatability. The NIRS measures were conducted using a cw-NIRS device. Secondly, this protocol was repeated in 10, healthy males and 10 non-insulin dependent sedentary males with T2D for characterisation and comparison of outcomes derived from cw-NIRS versus fd-NIRS. Thirdly, cw-NIRS and whole-body oxygen consumption (V̇O2) were measured in 24 men with T2D while performing incremental ramp cycle exercise to volitional exhaustion; in addition, biopsies of the VL were collected. Results: In study 1, mBF and mV̇O2 proportionally increased with intensity (0.55 to 7.68 ml∙min-1∙100ml-1 and 0.05 to 1.86 mlO2∙min-1∙100g-1, respectively) up to 25% MVC where it began to plateau at 30% MVC. For studies 1 and 2, a mBF/mV̇O2 ratio of ~5 was consistent for all exercise stages. For both Healthy and T2D groups, patterns of change and values for mBF and mV̇O2 during exercise were not substantially different between devices and were moderate to highly reproducible (ICC: 0.72-0.98). The mean typical error for exercise mBF and mV̇O2 with 90% Confidence Intervals was 0.41 (0.31-0.59) and 0.38 (0.29-0.55) for ND and T2D, respectively. Substantial differences were seen in ND and T2D, respectively, between CW- and FD-NIRS values for perfusion. Thirdly, the [HHb] primary phase during dynamic exercise was substantially correlated to V̇O2peak while the secondary phase was substantially correlated to measures of mitochondrial function. Conclusion: NIRS can reliably assess mBF and mV̇O2 responses at rest and during low-moderate exercise. The popular cw-NIRS device performed comparably to the more robust fd-NIRS when assessing mBF and mVO2 in both healthy and T2D populations, but cw-NIRS tended to overestimate perfusion, likely due to assumptions of constant scattering. Finally, combining NIRS with external respiration during continuous exercise has potential in investigating barriers to glucose disposal and exercise tolerance in T2D. Taken together, NIRS is a valid tool for applications in research, clinical diagnosis, and therapeutic assessment of skeletal muscle hemodynamics, microvascular, and respiratory plasticity

National eHealth system – platform for preventive, predictive and personalized diabetes care

National eHealth System, covering all citizens and all healthcare levels in Republic of Macedonia, was introduced in July 2013, has been internationally recognized System for successful reduction of waiting times and instrumental in the management of national healthcare resources. For the first time, National Diabetes Committee, formed in February 2015 according to the Law on healthcare and being overall responsible for the diabetes care in the country, was able to derive exact figures on the national diabetes prevalence from the System, instead of extrapolations used before, serving as a basis for development of strategies for prediction and prevention of diabetic complications, as well as for personalized diabetes care. Number of diabetes cases identified through the National eHealth System in June 2015 was 84,568 (4.02 % of total population), 36,119 males (3.42 % of total male population) and 48,449 females (4.61% of total female population). Age stratified diabetes prevalence was as follows: less than 20 years – 549 cases (0.11 % of respective population), 20-39 years – 3,202 (0.49 %), 40-59 years – 26,561 (4.58 %), 60-79 years – 48,470 (14.57 %), 80 years or more – 5,786 (12.96 %). Addition of parameters for metabolic control and diabetic complications in the System is under way, further facilitating the modeling of diabetes treatment, metabolic control and the outcomes. Inclusion of pre-diabetes patients (IGT and IFG) is also planned, thus providing opportunity to also focus healthcare activities for prevention of progression into overt type 2 diabetes

Novel methods for subcellular in vivo imaging of the cornea with the Rostock Cornea Module 2.0

The Rostock Cornea Module transforms a confocal laser scanning ophthalmoscope into a corneal confocal laser scanning microscope. In this thesis, an improved version, the Rostock Cornea Module 2.0, and its achieved results were demonstrated. These include a concave contact cap design to attenuate eye movements to improve 3D volume reconstruction, an oscillating focal plane to improve mosaicking of the subbasal nerve plexus, the integration of simultaneous optical coherence tomography, multiwavelength corneal imaging, the clinical usage, and the automated morphological characterization

Proceedings XXI Congresso SIAMOC 2021

XXI Congresso Annuale della SIAMOC, modalità telematica il 30 settembre e il 1° ottobre 2021. Come da tradizione, il congresso vuole essere un’occasione di arricchimento e mutuo scambio, dal punto di vista scientifico e umano. Verranno toccati i temi classici dell’analisi del movimento, come lo sviluppo e l’applicazione di metodi per lo studio del movimento nel contesto clinico, e temi invece estremamente attuali, come la teleriabilitazione e il telemonitoraggio